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  • Endocannabinoids mediate long-lasting behavioural and physiological changes in male rats induced by the repeated activation of the mesolimbic system by copulation to satiety
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-24
    Estefanía González-Morales; Gabriela Rodríguez-Manzo

    Sexually satiated male rats exhibit long-lasting physiological changes, suggestive of brain plasticity, the most conspicuous of which are a sexual behaviour inhibition and a generalised drug hypersensitivity. Copulation activates the mesolimbic circuit increasing dopamine (DA) release in the nucleus accumbens (NAcc) and, enhanced midbrain DA neuron activity promotes endocannabinoid (eCB) release in the ventral tegmental area (VTA). The objective of this work was to explore the possible participation of DA and/or eCB transmission in the induction of these two long-lasting phenomena. To this aim we analysed the effect of blocking DA or CB1 receptors during the process of copulation to exhaustion, on the expression 24 h later, of the sexual inhibitory state and the hypersensitivity to two different drugs: 8-OH-DPAT, a 5-HT1A receptor agonist, and yohimbine, an α2-adrenoceptor antagonist. Blockade of DA receptors failed to prevent these phenomena, while blockade of CB1 receptors interfered with the appearance of the sexual inhibition and the hypersensitivity to both drugs in the sexually satiated animals. Specific blockade of CB1 receptors in the VTA during copulation to satiety mimicked these results, suggesting that both eCB-mediated effects were exerted in this brain region. It is concluded that eCBs play a role in the induction of behavioural and physiological changes, triggered by copulation to satiety, by acting at the VTA, while increased NAcc DA levels appear not to contribute to the changes induced by intense copulation. Results pose sexual satiety as a useful model for the study of brain plasticity phenomena induced by natural rewards.

    更新日期:2020-01-24
  • Effects of aging on the motor, cognitive and affective behaviors, neuroimmune responses and hippocampal gene expression
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-24
    Gaurav Singhal; Julie Morgan; Magdalene C. Jawahar; Frances Corrigan; Emily J. Jaehne; Catherine Toben; James Breen; Stephen M. Pederson; Jim Manavis; Anthony J. Hannan; Bernhard T. Baune

    The known effects of aging on the brain and behavior include impaired cognition, increases in anxiety and depressive-like behaviors, and reduced locomotor activity. Environmental exposures and interventions also influence brain functions during aging. We investigated the effects of normal aging under controlled environmental conditions and in the absence of external interventions on locomotor activity, cognition, anxiety and depressive-like behaviors, immune function and hippocampal gene expression in C57BL/6 mice. Healthy mice at 4, 9, and 14 months of age underwent behavioral testing using an established behavioral battery, followed by cellular and molecular analysis using flow cytometry, immunohistochemistry, and quantitative PCR. We found that 14-month-old mice showed significantly reduced baseline locomotion, increased anxiety, and impaired spatial memory compared to younger counterparts. However, no significant differences were observed for depressive-like behavior in the forced-swim test. Microglia numbers in the dentate gyrus, as well as CD8+ memory T cells increased towards late middle age. Aging processes exerted a significant effect on the expression of 43 genes of interest in the hippocampus. We conclude that aging is associated with specific changes in locomotor activity, cognition, anxiety-like behaviors, neuroimmune responses and hippocampal gene expression.

    更新日期:2020-01-24
  • Overinhibition mediated by parvalbumin interneurons might contribute to depression-like behavior and working memory impairment induced by lipopolysaccharide challenge
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-24
    Mu-huo Ji; Ling Zhang; Ming-jie Mao; Hui Zhang; Jiao-jiao Yang; Li-li Qiu

    Systemic inflammation induces cognitive impairments via unclear mechanisms. Accumulating evidence has demonstrated that a subset of neurons that express parvalbumin (PV) play a critical role in regulation of cognitive and emotional behavior. Thus, the aim of the present study was to test whether disruption of PV interneuron mediates systemic inflammation–induced depression-like behavior and working memory impairment by lipopolysaccharide (LPS) challenge. Here we showed that LPS induces depression-like behavior and working memory impairment, coinciding with increased PV expression, enhanced GABAergic transmission, and impaired long-term potentiation (LTP) in the hippocampus. Notably, systemic administration of NMDA (N–methyl–D–aspartate) receptor (NMDAR) antagonist ketamine was able to interfere with PV expression and reverse depression-like behavior and working memory impairment, which is probably mediated by reversing impaired LTP. In addition, flumazenil, a competitive antagonist acting at the benzodiazepine binding site of the GABAA receptor, also ameliorated these abnormal behaviors. Collectively, our study added growing evidence to the limited studies that overinhibition mediated by PV interneurons might play a critical role in LPS–induced depression-like behavior and working memory impairment.

    更新日期:2020-01-24
  • Blunted satiety in fatty Zucker rats
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-24
    David P. Jarmolowicz; Tadd D. Schneider; Ale Carrillo; Jennifer L. Hudnall; Stefanie S. Stancato

    Levels of weight gain have hit an epidemic level with rates of overweight and obesity diagnoses topping all-time highs. Elevated body weight has been linked to increased rates of cardiac problems, blood pressure issues, and risk of developing type 2 diabetes. Leptin, a hormone produced by the body that is involved in energy balance by inhibiting hunger has been implicated as an underlying mechanism that differentially contributes to food-seeking motivation. Using a scientifically validated animal model of obesity, the fatty Zucker rat, which has mutated leptin receptor genes, leptin’s role in behavioral motivation can be assessed. Animals were on a 2 -h food access restriction with one-hour access to rewards in session and one hour of free-feeding access. Pre-session and post-session food access differences were evaluated in looking at motivation for food rewards during satiation while responding on differing levels of fixed-ratio schedules. The results showed robust differential behavior from satiation, demonstrating a basis for a biological mechanism involving leptin sensitivity that could underlie obesity. Although further experimentation is needed, understanding leptin could help bridge the gap in our understanding of satiation and non-satiation.

    更新日期:2020-01-24
  • Involvement of monoaminergic targets in the antidepressant- and anxiolytic-like effects of the synthetic alkamide Riparin IV: elucidation of further mechanisms through pharmacological, neurochemistry and computational approaches
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-24
    Danusio Pinheiro Sartori; Natália Ferreira de Oliveira; José Tiago Valentim; Daniel Moreira Alves da Silva; Auriana Serra Vasconcelos; Iris Cristina Maia Oliveira; Raquell de Castro Chaves; Victor Celso Cavalcanti Capibaribe; Alyne Mara Rodrigues de Carvalho; Manoela de Oliveira Rebouças; Danielle Macêdo; Adriano José Maia Chaves Filho; Marta Maria de França Fonteles; Stanley Juan Chavez Gutierrez; José Maria Barbosa-Filho; Melina Mottin; Carolina Horta Andrade; Francisca Cléa Florenço de Sousa
    更新日期:2020-01-24
  • The Medial Agranular Cortex Mediates Attentional Enhancement of Prepulse Inhibition of the Startle Reflex
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-24
    Qingxin Meng; Yu Ding; Liangjie Chen; Liang Li

    The startle reflex, which interferes with on-going cognitive/behavioral activities, is of important protective function for humans and animals. Prepulse inhibition (PPI), as an operational measure of sensorimotor gating, is the suppression of the startle reflex in response to an intense startling stimulus (pulse) when this startling stimulus is shortly preceded by a weaker non-startling stimulus (prepulse). In both humans and laboratory animals, PPI can be enhanced by facilitating selective attention to the prepulse, suggesting that higher-order cognitive/perceptual processes modulate PPI. It has been well known that both the cholinergic system located in the basal forebrain and the deep layers of the superior colliculus in the PPI-mediating circuit are top-down modulated by the medial agranular cortex (AGm), which is a subdivision of the medial prefrontal cortex (PFC) and has wide axonal connections with both cortical regions (including the posterior parietal cortex) and subcortical structures critical for attention/orientation processes. This study investigated whether the AGm is involved in attentional modulation of PPI. The results showed that PPI was enhanced by fear conditioning of the prepulse, and then further enhanced by perceived spatial separation between the conditioned prepulse and a back-ground masking noise based on the auditory precedence effect. Bilateral injection of 2-mM kynurenic acid, a broad spectrum antagonist of glutamate receptors, into the AGm, but not the primary somatosensory cortex, eliminated these two types of attentional enhancement of PPI. Thus, the AGm plays a role in facilitating attention to the prepulse and is involved in the top-down modulation of PPI.

    更新日期:2020-01-24
  • Differential Effects of Hunger on Cerebral Blood Flow in Healthy Adolescents
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-23
    Céline Charroud; Nicolas Menjot de Champfleur; Emily Sanrey; Josef Pfeuffer; Jérémy Deverdun; Emmanuelle Le Bars; Philippe Coubes

    Adolescence represents a key developmental period in terms of both mood and overweight and is linked to disturbed eating behavior. Therefore, it is essential to investigate the basis of food intake in healthy adolescents by considering mood impacts which remain largely unexplored. Hence this study aims to investigate the impact of hunger and mood on cerebral blood flow (CBF) changes in healthy adolescents. Fifteen participants underwent two MRI sessions including a 3D pseudo-continuous arterial spin labeling sequence: pre-lunch (hunger) and post-lunch (satiety). Mood was assessed using the Multiscore Depression Inventory for Children. We found higher CBF values in the posterior insula in response to hunger compared to satiety, an area of the brain which contributes to the anticipation and motivation of feeding. In response to satiation, we observed higher CBF values in the precuneus, lingual gyrus and cuneus which are involved in the aspects of response inhibition related to food intake. Furthermore, we show that correlation between mood assessment and CBF is modulated by appetite in the precuneus, anterior cingulate gyrus, anterior orbitofrontal gyrus, occipital gyrus and cuneus, suggesting that participants affected by depressed mood could use ruminative processing in order to evaluate the reward of an upcoming meal.

    更新日期:2020-01-24
  • Mirogabalin prevents repeated restraint stress-induced dysfunction in mice
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-23
    Takashi Iwai; Akinori Kikuchi; Misa Oyama; Shun Watanabe; Mitsuo Tanabe

    Gabapentinoids, which are the common analgesics, are also thought to be an effective treatment for anxiety disorder, which is one of several psychiatric disorders triggered and exacerbated by stress. The aim of the present study was to investigate whether mirogabalin, a recently launched gabapentinoid, protects multiple brain functions against repeated restraint stress. Adult male ddY mice were restrained for 7 days (repeated restraint stress: 2 h/day) or for 30 min (single restraint stress). Mirogabalin (intraperitoneal, intracerebroventricular or intrahippocampal injection) was administered prior to the restraint stress. Y-maze, elevated-plus maze and c-Fos immunohistochemistry were performed to evaluate learning function, anxiety levels and hippocampal neuronal activities, respectively, after the 7th day of the repeated restraint stress. Intestinal function was evaluated in terms of defecation, which was scored after the 5th day of repeated restraint stress and by the number of fecal pellets excreted after a single session of restraint stress. Repeated restraint stress induced memory dysfunction, anxiety-like behavior, an abnormal defecation score and increased hippocampal c-Fos expression. These changes were prevented by systemic administration of mirogabalin. Abnormal defecation was also induced by single restraint stress, and was inhibited by both systemic and central administration of mirogabalin, suggesting that the effect on the intestinal function was also mediated via the central nervous system. Enhancement of c-Fos expression by repeated stress was decreased by intrahippocampal injection of mirogabalin. Together, these observations suggest that mirogabalin protects multiple brain functions from repeated stress, which may be mediated by inhibition of hippocampal neuron hyperactivation.

    更新日期:2020-01-23
  • Is there a relationship between low-grade systemic inflammation and cognition in healthy people aged 60-75 years?
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-22
    M.T. Fard; L. Cribb; K. Nolidin; K. Savage; K. Wesnes; C. Stough

    Although inflammation has been associated with cognitive impairment in dementia, less is known about its role in the cognition of middle to older aged healthy people. This study utilised baseline data from the Australian Research Council Longevity Intervention (ARCLI) trial to investigate the relationship between markers of systemic inflammation (TNF-α, IL-6, IL-1β, INF-γ, IL-2, IL-4, IL-10 and hsCRP) and cognitive function in 286 healthy volunteers aged 60-75 years. We assessed cognitive functioning across domains including attention, speed of memory, working memory and episodic memory using the Cognitive Drug Research test battery. Only IFN-γ was related to cognitive function, being associated with greater odds of having low continuity of attention (log2 IFN-γ OR, 1.46; 95% CI, 1.18–1.85). The relationship between episodic memory, speed of memory and inflammation varied with BMI. In high BMI participants, increased inflammation was associated with worse cognitive function, while this association was reversed in those with low BMI. Outside of the influence of IFN-γ on attention, low-grade systemic inflammation was not robustly associated with cognitive function in this sample of middle to older aged healthy people. Further research is required to understand the role of BMI in the intersection of inflammation and cognitive function.

    更新日期:2020-01-22
  • Critical role of protein kinase G in the long-term balance between defensive and appetitive behaviors induced by aversive stimuli in Aplysia
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-22
    Ruma Chatterji; Sarah Khoury; Emanuel Salas; Marcy L. Wainwright; Riccardo Mozzachiodi

    This study investigated the signaling cascades involved in the long-term storage of the balance between defensive and appetitive behaviors observed when the mollusk Aplysia is exposed to aversive experience. In Aplysia, repeated trials of aversive stimuli induce concurrent sensitization of defensive withdrawal reflexes and suppression of feeding for at least 24 h. This long-term storage of the balance between withdrawal reflexes and feeding is sustained, at least in part, by increased excitability of the tail sensory neurons (SNs) controlling the withdrawal reflexes, and by decreased excitability of feeding decision-making neuron B51. Nitric oxide (NO) is required for the induction of both long-term sensitization and feeding suppression. At the cellular level, NO is also required for long-term decreased B51 excitability but not for long-term increased SN excitability. Here, we characterized the signaling cascade downstream of NO contributing to the long-term storage of the balance between withdrawal reflexes and feeding. We found protein kinase G (PKG) necessary for both long-term sensitization and feeding suppression, indicating that a NO-PKG cascade governs the long-term storage of the balance between defensive and appetitive responses in Aplysia. The role of PKG on feeding suppression was paralleled at the cellular level where a cGMP-PKG pathway was required for long-term decreased B51 excitability. In the defensive circuit, the cGMP-PKG pathway was not necessary for long-term increased SN excitability, suggesting that other cellular correlates of long-term sensitization might depend on the GMP-PKG cascade to sustain the behavioral change.

    更新日期:2020-01-22
  • Hippocampal overexpression of SGK1 ameliorates spatial memory, rescues Aβ pathology and actin cytoskeleton polymerization in middle-aged APP/PS1 mice
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-22
    Biyao Lian; Mengying liu; Zhen Lan; Tao Sun; Zhaoyou Meng; Qing Chang; Zhi Liu; Jiqiang Zhang; Chengjun Zhao

    The increasing occurrence and ineffective treatment of Alzheimer’s disease (AD) has become one of the major challenges of the world. Limited studies have shown that serum- and glucocorticoid-inducible kinase 1 (SGK1) is involved in spatial memory formation and consolidation, but its role in AD-like spatial memory impairment and the related mechanisms are not clear. In this study, we first examined the age-related changes of SGK1 in the hippocampus of female APP/PS1 (AD) mice. Based on the finding and our previous finding that significant spatial memory impairment was detected in 8-month old AD mice, SGK1-overexpressing AAV (oSGK1) was constructed and injected into the hippocampus of 9-month old AD mice. One month later, the behavior alterations, Aβ production and deposit as well as changes of CA1 spine density and selected actin polymerization remodeling proteins were examined. The results showed that significant decrease of SGK1 was detected in 10-month old AD mice. The spatial memory impairment, the production and deposit of Aβ were reversed by oSGK1. Levels of hippocampal ADAM10 (α-secretase) and IDE (Aβ degradase), actin remodeling related proteins Rictor, Rac1, Cdc42 and Profilin-1 were significantly increased after oSGK1 treatment while hippocampal BACE1 (γ-secretase) and Cofilin remained unchanged. Taken together, our findings demonstrated a pivotal role of SGK1 in the treatment of AD-related memory impairment through upregulation of non- amyloidogenic processing of APP and degradation of Aβ, increase in spine plasticity related proteins, indicating increase in hippocampal SGK1 may be a potent therapeutic target against AD.

    更新日期:2020-01-22
  • Developmental effects of daily food availability times on song behaviour and neuronal plasticity of song-control system in male zebra finches
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-21
    Ila Mishra; Twinkle Batra; Abhilash Prabhat; Neha Agarwal; Sanjay Kumar Bhardwaj; Vinod Kumar

    Food availability is a major ecological factor and affects body condition and sexual traits. Here, we investigated whether males’ song behaviour, a trait for female mate choice, was sensitive to the food availability period and its timing in songbirds. We manipulated daily food availability to 4 h in the morning or evening, with controls on food ad libitum, and assessed its effects on song behaviour and forebrain song control system in male zebra finches that were held as adult (parent) or offspring (since birth) at 24 ± 2 °C under 12 h daily photoperiod. Food restriction significantly affected both temporal and spectral features of daily song in offspring, not the parent. In offspring, we found reduced mesor (mean 24-h levels), attenuated amplitude (daily maxima relative to mesor) and altered acrophase (estimated time of daily maxima) of 24-h rhythm, and reduced motif length (in morning-fed), per motif unique syllables and an enhanced song pitch (in evening-fed). There was also a positive correlation of motif length with cheek patch and plasma testosterone levels, and of per motif syllables with cheek patch and daily activity levels in offspring. Among main song controlling forebrain nuclei, LMAN and HVC were reduced in size, and Area X and HVC showed decreased neuronal recruitment in offspring on food restrictions. These results demonstrate the importance of daily food availability and its timing in determining males’ sexual signals, and support growing evidence that among vertebrates well-fed males contain reproductive traits that females use for its mate choice.

    更新日期:2020-01-22
  • Nicotine induces resilience to chronic social defeat stress in a mouse model of water pipe tobacco exposure by activating BDNF signaling
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-21
    Mohamad Khalifeh; Rouba Hobeika; Lauretta El Hayek; Joelle Saad; Fadi Eid; Reine El-Khoury; Litsa-Maria Ghayyad; Vanessa Jabre; Patrick Nasrallah; Nour Barmo; Joseph S. Stephan; Rony Khnayzer; Christian Khalil; Sama F. Sleiman

    The purpose of this study was to investigate how nicotine in the context of water pipe tobacco smoking (WTS) affects depression and anxiety-like behaviors associated with chronic social defeat stress (CSDS). Male C57BL/6 J mice were exposed to WTS or received intraperitoneal injections of nicotine for thirty days then subjected to CSDS for ten days. During CSDS, mice were exposed to WTS or received nicotine injections. The social interaction and open-field tests were used to classify animals as resilient or susceptible to stress and to evaluate their anxiety-like behavior. After behavioral testing, mice continued to be exposed to WTS/nicotine for ten days and their behavior was reexamined. The involvement of brain derived neurotrophic factor signaling in the nicotine-mediated effects was assessed with the tropomyosin receptor kinase B (TRKB) inhibitor, ANA-12. We found that WTS promotes resilience to stress and rescues social avoidance. Even though WTS initially decreased anxiety-like behaviors, prolonged exposure after the completion of CSDS significantly induced anxiety-like behaviors. Finally, we showed that nicotine mediates the effects of WTS only on resilience to stress by increasing BDNF and TRKB levels and signaling. Our results suggest that the pathways mediating resilience to stress and anxiety are distinct and that nicotine mediates the effects of WTS on social behavior, but not anxiety, by activating BDNF signaling. Significance statement: This study reports the positive effect of WTS and nicotine on social behavior. Furthermore, it shows the negative effects of prolonged WTS on anxiety-like behaviors and suggests that these effects are not necessarily mediated by nicotine. Finally, it identifies BDNF/TRKB signaling pathway as a major mediator of the positive effects of nicotine on social interaction. As a result, this work emphasizes the importance of considering the activation status of this signaling pathway when developing smoking cessation strategies.

    更新日期:2020-01-22
  • Chronic Repeated Predatory Stress Induces Resistance to Quinine Adulteration of Ethanol in Male Mice
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-21
    Gladys A. Shaw; Maria Alexis M. Bent; Kimaya R. Council; A. Christian Pais; Ananda Amstadter; Jennifer T. Wolstenholme; Michael F. Miles; Gretchen N. Neigh

    Background Trauma related psychiatric disorders, such as posttraumatic stress disorder (PTSD), and alcohol use disorder (AUD) are highly comorbid illnesses that separately present an opposing, sex-specific pattern, with increased prevalence of PTSD in females and increased prevalence of AUD diagnoses in males. Likewise, PTSD is a risk factor in the development of AUD, with conflicting data on the impact of sex in the comorbid development of both disorders. Because the likelihood of experiencing more than one traumatic event is high, we aim to utilize chronic repeated predatory stress (CRPS) to query the extent to which sex interacts with CRPS to influence alcohol consumption, or cessation of consumption. Methods Male (n = 16) and female (n = 15) C57BL/6 J mice underwent CRPS or daily handling for two weeks during adolescence (P35-P49) and two weeks during adulthood (P65-P79). Following the conclusion of two rounds of repeated stress, behavior was assessed in the open field. Mice subsequently underwent a two-bottle choice intermittent ethanol access (IEA) assessment (P90-131) with the options of 20% ethanol or water. After establishing drinking behavior, increasing concentrations of quinine were added to the ethanol to assess the drinking response to adulteration of the alcohol. Results CRPS increased fecal corticosterone concentrations and anxiety-like behaviors in the open field in both male and female mice as compared to control mice that had not been exposed to CRPS. Consistent with previous reports, we observed a sex difference in alcohol consumption such that females consumed more ethanol per gram of body mass than males. In addition, CRPS reduced alcohol aversion in male mice such that higher concentrations of quinine were necessary to reduce alcohol intake as compared to control mice. CRPS did not alter alcohol-related behaviors in female mice. Conclusion Collectively, we demonstrate that repeated CRPS can induce anxiety-like behavior in both sexes but selectively influences the response to ethanol adulteration in males.

    更新日期:2020-01-22
  • Resting-state effective connectivity in the motive circuit of methamphetamine users: a case controlled fMRI study
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-21
    Meysam Siyah Mansoory; Vahid Farnia

    Methamphetamine (MA) and other psychostimulants target the motive circuit of the brain, which is involved in reward, behavioral sensitization, and relapse to drug-seeking/taking behavior. In spite of this fact, the data regarding the effective connectivity (EC) in this circuit among MA users is scarce. The present study aimed to assess resting-state EC in the motive circuit of MA users during abstinence using the fMRI technique. Seventeen MA users after abstinence and 18 normal controls were examined using a 3 T Siemens fMRI scanner. After extracting time series of the motive circuit, EC differences in the motive circuit were analyzed using dynamic causal modeling (DCM). The findings revealed that abstinent MA users had an enhanced EC from the prefrontal cortex (PFC) to the ventral palladium (VP) (PFC→VP) and on the mediodorsal thalamus (MD) self-loop (MD→MD), but they showed a decreased connectivity on the VP self-loop (VP→VP) compared to healthy controls. The findings suggest that abstinent MA users may suffer from a limited pathology in connectivity within the motive circuit involved in reward, behavioral sensitization, and relapse. The enhanced PFC→VP seems to be a compensatory mechanism to control or regulate the subcortical regions involved in reward and behavioral sensitization. Furthermore, the enhanced connectivity on the MD self-loop and the decreased connectivity on the VP self-loop in abstinent MA users may, at least partially, affect the output of the limbic system, which can be seen in the behavioral sensitization and relapse processes. Nonetheless, further investigation in this area is strongly recommended to elucidate the exact mechanisms involved.

    更新日期:2020-01-22
  • Comparing Different EEG Connectivity Methods in Young Males with ASD
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-20
    Kimaya Sarmukadam; Vicki Bitsika; Christopher F. Sharpley; Mary M.E. McMillan; Linda L. Agnew

    Although EEG connectivity data are often used to build models of the association between overt behavioural signs of Autism Spectrum Disorder (ASD) and underlying brain connectivity indices, use of a large number of possible connectivity methods across studies has produced a fairly inconsistent set of results regarding this association. To explore the level of agreement between results from five commonly-used EEG connectivity models (i.e., Coherence, Weighted Phased Lag Index- Debiased, Phase Locking Value, Phase Slope Index, Granger Causality), a sample of 41 young males with ASD provided EEG data under eyes-opened and eyes-closed conditions. There were relatively few statistically significant and/or meaningful correlations between the results obtained from the five connectivity methods, arguing for a re-estimation of the methodology used in such studies so that specific connectivity methods may be matched to particular research questions regarding the links between neural connectivity and overt behaviour within this population.

    更新日期:2020-01-21
  • A Simple Three Layer Excitatory-Inhibitory Neuronal Network for Temporal Decision-Making
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-20
    Mustafa Zeki; Fuat Balci

    Humans and animals do not only keep track of time intervals but they can also make decisions about durations. Temporal bisection is a psychophysical task that is widely used to assess the latter ability via categorization of durations as short or long. Many existing models of performance in temporal bisection primarily account for choice proportions and tend to overlook the associated response times. We propose a time-cell neural network that implements both interval timing and temporal categorization. The proposed model can keep track of time intervals based on lurching wave activity, it can learn the reference durations along with their association with different categorization responses, and finally, it can carry out the comparison of arbitrary intermediate durations to the reference durations. We compared the model's predictions about choice behavior and response times to the empirical data previously gathered from rats. We showed that this time-cell neural network can predict the canonical behavioral signatures of temporal bisection performance. Specifically, a) the proposed model can account for the sigmoidal relationship between the probability of the long choices and the test durations, b) the superimposition of choice functions on a relative time scale, c) the localization of the point of subjective equality at the geometric mean of the reference durations, and d) the differential modulation of short and long categorization response times as a function of the test durations.

    更新日期:2020-01-21
  • Circadian modulation of motivation in mice
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-17
    Julieta Acosta; Ivana L. Bussi; Macarena Esquivel; Christian Höcht; Diego A. Golombek; Patricia V. Agostino

    Most living organisms have a circadian timing system adapted to optimize the daily rhythm of exposure to the environment. This circadian system modulates several behavioral and physiological processes, including the response to natural and drug rewards. Food is the most potent natural reward across species. Food-seeking is known to be mediated by dopaminergic and serotonergic transmission in cortico-limbic pathways. In the present work, we show evidence of a circadian modulation of motivation for food reward in young (4-months old) and aged (over 1.5 years old) C57BL/6 mice. Motivation was assayed through the progressive ratio (PR) schedule. Mice under a 12:12 light/dark (LD) cycle exhibited a diurnal rhythm in motivation, becoming more motivated during the night, coincident with their active phase. This rhythm was also evident under constant dark conditions, indicating the endogenous nature of this modulation. However, circadian arrhythmicity induced by chronic exposure to constant light conditions impaired the performance in the task causing low motivation levels. Furthermore, the day/night difference in motivation was also evident even without caloric restriction when using a palatable reward. All these results were found to be unaffected by aging. Taken together, our results indicate that motivation for food reward is regulated in a circadian manner, independent of the nutritional status and the nature of the reward, and that this rhythmic modulation is not affected by aging. These results may contribute to improve treatment related to psychiatric disorders or drugs of abuse, taking into account potential mechanisms of circadian modulation of motivational states.

    更新日期:2020-01-17
  • Effect of Brightness of Visual Stimuli on EEG Signals
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-17
    Kübra Eroğlu; Temel Kayıkçıoğlu; Onur Osman

    The aim of this study was to examine brightness effect, which is the perceptual property of visual stimuli, on brain responses obtained during visual processing of these stimuli. For this purpose, brain responses of the brain to changes in brightness were explored comparatively using different emotional images (pleasant, unpleasant and neutral) with different luminance levels. In the study, electroencephalography recordings from 12 different electrode sites of 31 healthy participants were used. The power spectra obtained from the analysis of the recordings using short time Fourier transform were analyzed, and a statistical analysis was performed on features extracted from these power spectra. Statistical findings were compared with those obtained from behavioral data. The results showed that the brightness of visual stimuli affected the power of brain responses depending on frequency, time and location. According to the statistically verified findings, the increase in the brightness of pleasant and neutral images increased the average power of responses in the parietal and occipital regions whereas the increase in the brightness of unpleasant images decreased the average power of responses in these regions. Moreover, the statistical results obtained for unpleasant images were found to be in accordance with the behavioral data. The results revealed that the brightness of visual stimuli could be represented by changing the activity power of the brain cortex. The findings emphasized that the brightness of visual stimuli should be viewed as an important parameter in studies using emotional image techniques such as image classification, emotion evaluation and neuro-marketing.

    更新日期:2020-01-17
  • Transcranial direct current stimulation improves risky decision making in women but not in men: a sham-controlled study
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-17
    J.J. León; A. Sánchez-Kuhn; P. Fernández-Martín; M.A. Páez-Pérez; C. Thomas; A. Datta; F. Sánchez-Santed; P Flores

    Behavioral and anatomical sex-related differences have been traditionally found in decision-making processes assessed by Iowa Gambling Task (IGT). So far, the administration of transcranial direct current stimulation (tDCS) over orbitofrontal regions has shown an enhancing effect over decision-making. However, it is unknown whether there is a sex-dependent effect of stimulation in decision-making, a key question considering previous differences between men and women in IGT and the influence of individual differences in tDCS. The present study examines, at first time, the interaction between sex and tDCS in decision-making. For that aim, in a first experimental phase, ninety-two healthy participants performed the IGT. In a second phase, sixty-one participants received 20 min of anodal or sham tDCS over the right orbitofrontal cortex (rOFC) in a single-session pre-post sham-controlled study. To support the focality of the montage, a Stop Signal Task (SST) was used as a control task and also a numerical simulation of current flow distribution was performed. According to literature, in the first phase, results showed that men outperformed women in the IGT. In the second phase, the stimulation varied the IGT performance according to a sex specific manner: anodal tDCS increased the IGT performance in women, while in men; the stimulation did not produce any effect. Results were mediated by sex-specific morphological differences. These results highlight the necessity to consider the interaction of sex with the effect of the stimulation in future tDCS protocols, specifically in future clinical studies.

    更新日期:2020-01-17
  • The effect of erythropoietin on electroconvulsive stimulation induced cognitive impairment in rats
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-16
    Kristian Kjær; Martin Balslev Jørgensen; Ida Hageman; Kamilla Woznica Miskowiak; Gitta Wörtwein

    Electroconvulsive therapy (ECT) is the most effective and fast-acting treatment for severe depression but associated with troublesome cognitive side-effects. Systemically administered erythropoietin (EPO) crosses the blood-brain-barrier and is a promising treatment for cognitive dysfunction in a wide array of neuropsychiatric and neurological disorders. In this study we trained rats to locate a submerged platform in a water maze and then subjected them to electroconvulsive stimulations (ECS, the rodent equivalent to ECT) and EPO treatment. We then analysed their ability to remember and relearn the location of the platform. In addition, we examined “wall-clinging” (thigmotaxis), a behavioural indicator of stress. ECS caused significant deficit in a probe trial administered after three weeks (nine stimulations) as well as one week (six stimulations) of treatment, indicative of induction of retrograde amnesia. ECS had no effect on relearning of the water maze task or performance in a subsequent probe trial. EPO treatment did not ameliorate the ECS-induced retrograde amnesia, but after nine ECS stimulations the animals that had received EPO relearned the position of the hidden platform faster than the animals that had not. We also found EPO to decrease “wall-clinging” behaviour, suggesting an effect of EPO on the stress response in rats. Thus, we establish the Morris Water Maze as a suitable model for ECS-induced memory loss in rats and provide some evidence for potential beneficial effects of EPO.

    更新日期:2020-01-16
  • Aberrant resting-state interhemispheric functional connectivity in patients with postpartum depression
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-16
    Shufen Zhang; Wei Wang; Gang Wang; Bo Li; Liping Chai; Jianping Guo; Xin Gao

    The aim of this study is to investigate the alterations of interhemispheric functional connectivity in patients with postpartum depression (PPD) during resting state, and their potential correlations with clinical severity. Twenty- eight patients with PPD and twenty-five matched healthy postpartum (HP) women within 4 weeks after delivery were recruited and performed resting-state functional magnetic resonance imaging(fMRI) scans. Voxel-mirrored homotopic connectivity (VMHC), which is useful for exploring interhemispheric functional connectivity, and has been widely utilized to identify abnormal functional connectivity between the symmetrical brain regions in many diseases, was calculated in the present study, and intergroup VMHC differences in the voxel manner were analyzed. Correlations between VMHC values and clinical variables were also analyzed. Compared with HP, patients with PPD exhibited significantly decreased VMHC values in bilateral dorsomedial prefrontal cortex (dmPFC), dorsal anterior cingulate cortex (dACC) and orbitofrontal cortex (OFC). Furthermore, VMHC values within the dmPFC negatively correlated with the Edinburgh postpartum depression scale (EPDS) score. These findings suggested that functional coordination between several homotopic brain regions were impaired in patients with PPD. This study provided evidences of aberrant interhemispheric connectivity within brain regions involved in the maternal care network in PPD, and may contribute to the further understanding of the neural mechanism underlying PPD.

    更新日期:2020-01-16
  • MODERATE INTENSITY INTERMITTENT EXERCISE UPREGULATES NEUROTROPHIC AND NEUROPROTECTIVE GENES EXPRESSION AND INHIBITS PURKINJE CELL LOSS IN THE CEREBELLUM OF OVARIECTOMIZED RATS
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-15
    Saidah Rauf; Marsetyawan HNE Soesatyo; Denny Agustiningsih; Ginus Partadiredja

    Decreases in estrogen levels due to menopause or ovariectomy may disrupt cerebellar motor functions. This study aimed at investigating the effects of Moderate Intensity Intermittent Exercise (MIEx) on the cerebellum of ovariectomized rats by analyzing neurotrophic and neuroprotective markers, as well as cerebellar motor functions. Thirty-two female Sprague Dawley rats were divided into four groups, i.e. Sham and ovariectomy (Ovx) of non-MIEx (NMIEx) groups, and Sham and Ovx with MIEx groups. MIEx was performed 5 days a week on treadmill for 6 weeks. Motor functions were assessed using rotarod, footprint, open field, and wire hanging tests. Real-time polymerase chain reaction was performed to determine messenger RNA (mRNA) expressions of Pgc-1α, BDNF, synaptophysin, Bcl-2, and Bax. Unbiased stereology was used to estimate the total number of cerebellar Purkinje cells. The Ovx MIEx group had higher Pgc-1α and Bcl-2 mRNA expressions, and number of Purkinje cells, but lower Bax mRNA expression than the Ovx NMIEx group. All motor functions of MIEx groups were better than the Sham and Ovx groups without MIEx. Motor functions on rotarod task, OFT, and FPT correlated significantly with the mRNAs expression of Bcl-2, Bax, BDNF, synaptophysin, Pgc-1α, and the number of cerebellar Purkinje cells in ovariectomized rats. MIEx improves cerebellar neurotrophic and neuroprotective markers, as well as motor functions of ovariectomized rats.

    更新日期:2020-01-15
  • Redefining the Relationship Between Effort and Reward: Choice-Execution Model of Effort-Based Decisions
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-15
    Agata Ludwiczak; Magda Osman; Marjan Jahanshahi

    Neuroscientific studies reliably demonstrate that rewards play a crucial role in guiding our choices when confronted with different effortful actions we could make. At the same time, psychological and economic research shows that effort we exert is not reliably predicted by the rewards we end up receiving. Why the mismatch between the two lines of evidence? Inspired by neuroscientific literature, we argue that value-based models of decision-making expose the complexity of the relationship between effort and reward, which changes between two crucial stages of the effort-based decision making process: Choice (i.e. action selection) and Execution (i.e. action execution involving actual effort exertion). To test this assumption, in the present study we set up two experiments (E1: N = 72, E2: N = 87), using a typical neuroscientific effort-based decision-making task. The findings of these experiments reveal that when making prospective choices, rewards do guide the level of effort people are prepared to exert, consistent with typical findings from Neuroscience. At a later stage, during execution of effortful actions, performance is determined by the actual amount of effort that needs to be exerted, consistent with psychological and behavioral economic research. We use the model we tested and the findings we generated to highlight critical new insights into effort-reward relationship, bringing different literatures together in the context of questions regarding what effort its, and the role that values play.

    更新日期:2020-01-15
  • Sensitized corticosterone responses do not mediate the enhanced fear memories in chronically stressed rats
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-15
    Adam C. Kulp; Brett Lowden; Sachi Chaudhari; Cassidy Ridley; James Krzoska; David Barnard; Devanshi Mehta; John Johnson

    Following a stressful event, the hypothalamus-pituitary-adrenal axis mediates the release of the stress hormone cortisol (corticosterone in rodents; CORT). Elevated CORT binds to glucocorticoid receptors to mediate physiological responses including facilitating memory formation. Previous work from our laboratory demonstrated that male rats exposed to chronic stress demonstrate enhanced contextual fear memories and sensitized CORT responses to subsequent stress exposure; however, this is unknown in female rats. The experiments here tested whether chronic stress enhances fear memory formation in female rats and whether the sensitized CORT response in chronic stress rats contributes to their enhanced fear memory. Studies first examined CORT responses to contextual fear conditioning in male and female rats and examined whether chronic stress enhanced the formation of contextual fear memories 24 hrs later. Studies then used metyrapone, a CORT synthesis inhibitor, to investigate whether blockade of plasma CORT would eliminate the chronic stress-induced enhancement in contextual fear memory. Results show that female rats have greater CORT responses than males, and chronic stress sensitizes the CORT response to fear conditioning in both sexes. However, female rats do not show enhanced contextual fear memory following chronic stress. Chronically stressed male rats show greater memory acquisition and show greater contextual fear memory 24 hrs later following fear conditioning. Metyrapone dampens contextual fear memory in all rats but does not eliminate the enhancement in freezing behavior in chronic stress rats. Collectively, these studies indicate sensitized CORT responses in chronically stressed rats is likely not the mechanism by which chronic stress facilitates memory formation.

    更新日期:2020-01-15
  • Modulating activity in the dorsolateral prefrontal cortex alter corruption behavior: a transcranial direct current stimulation study
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-13
    Bonai Fan; Wenhao Mao; Jia Jin; Qingguo Ma

    Corruption behavior has gained worldwide concern for its great harmfulness to public society. In order to reduce corruption, researchers have carried out numerous studies on corrupt prevention. Researchers found that except for external supervision, the internal factor such as moral judgment also have an impact on corruption behavior. Previous brain imaging and stimulation studies suggested that dorsolateral prefrontal cortex (DLPFC) is critical brain area which integrates emotional and cognitive process of moral judgments. Therefore, in the current study, we applied tDCS (transcranial direct current stimulation) over DLPFC to investigated the modulation effect of cortical excitability on corruption behavior. According to the characteristics of corruption, we designed an incomplete information invest game task based on trust game, then adopted a between-subject design to compare participants’ corruption rate and reaction time (RT) among right anodal/left cathodal, left anodal/right cathodal and sham tDCS. The results showed that, in contrast to sham stimulation, left anodal/right cathodal tDCS reduced corruption rate both in high and low entrusted amount while right anodal/left cathodal tDCS only prolonged subjects’ reaction time (RT) of dishonest response only in high entrusted amount. A possible explanation for the results of current study is that the left DLPFC is associated with the emotional process, which influenced the moral intuition aspect of moral judgment and reflected in the change of immoral behavior rate. While the right DLPFC is associated with cognitive control, which influenced the moral reasoning aspect of moral judgment and reflected in the change of reaction time. This explanation is also consistent with the Emotion-Evoked Collective Corruption Model and dual process theory of brain function.

    更新日期:2020-01-13
  • Left-right functional difference of the rat dorsal hippocampus for short-term memory and long-term memory
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-11
    Yukitoshi Sakaguchi; Yoshio Sakurai

    The existence of left-right hemispheric differences has been suggested not only in humans but also in rodents. In recent studies, left-right anatomical and functional differences of the rodent hippocampus have been revealed. However, there is only one report investigating the left-right difference for short-term memory (STM), and the left-right difference for long-term memory (LTM) is not consistent among previous studies. Therefore, we examined the effects of unilateral hippocampal lesion and stimulation on the formation of STM and LTM in rats. Our results showed that the right, but not the left, hippocampal lesion impaired STM performance, evaluated by the alternation rate in the spontaneous alternation test and the novel-arm choice rate in the novelty preference test. In addition, electrical stimulation of the left, but not the right, hippocampus immediately before the tests impaired STM performance. On the other hand, the left, but not the right, hippocampal lesion impaired the LTM performance, evaluated by the discrimination index in the object recognition test. In addition, the stimulation of the left, but not the right, hippocampus impaired LTM performance. These results suggest that both the left and right hippocampi are involved in STM formation, and the right hippocampus has a facilitating role while the left hippocampus has a suppressing role for STM. On the other hand, LTM may be driven correctly only by the left hippocampus with appropriate level of neural activity. The left and right hippocampi of rodents may work in different mechanisms depending on the demand for STM and LTM.

    更新日期:2020-01-13
  • Maladaptive Avoidance Patterns in Parkinson’s Disease are Exacerbated by Symptoms of Depression
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-11
    Jony Sheynin; Irina Baetu; Lyndsey E. Collins-Praino; Catherine E. Myers; Robyn Winwood-Smith; Ahmed A. Moustafa

    disease (PD) is a chronic, progressive neurodegenerative disorder, characterized by a loss of dopaminergic neurons in the substantia nigra pars compacta. Given that dopamine is critically involved in learning and other cognitive processes, such as working memory, dopamine loss in PD has been linked both to learning abnormalities and to cognitive dysfunction more generally in the disease. It is unclear, however, whether avoidance behavior is impacted in PD. This is significant, as this type of instrumental behavior plays an important role in both decision-making and emotional (dys)function. Consequently, the aim of the present study was to examine avoidance learning and operant extinction in PD using a computer-based task. On this task, participants control a spaceship and attempt to shoot an enemy spaceship to gain points. They also learn to hide in safe areas to protect from (i.e., avoid) aversive events (on-screen explosions and point loss). The results showed that patients with PD (N = 25) acquired an avoidance response during aversive periods to the same extent as healthy age- and education-matched controls (N = 19); however, patients demonstrated greater hiding during safe periods not associated with aversive events, which could represent maladaptive generalization of the avoidance response. Furthermore, this impairment was more pronounced during the extinction phase, and in patients who reported higher levels of depression. These results demonstrate for the first time that PD is associated with maladaptive avoidance patterns, which could possibly contribute to the emergence of depression in the disease.

    更新日期:2020-01-13
  • Monoamine Oxidase A Genotype and Methylation Moderate the Association of Maltreatment and Aggressive Behaviour
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-10
    David Checknita; Megha Bendre; Tomas J. Ekström; Erika Comasco; Jari Tiihonen; Sheilagh Hodgins; Kent W. Nilsson

    Background The association between childhood maltreatment and subsequent aggressive behaviour is modified by monoamine oxidase A (MAOA) functional polymorphism (MAOA-uVNTR) genotype, MAOA-Long (MAOA-L) in females, MAOA-Short (MAOA-S) in males. Childhood maltreatment is associated with differential DNA methylation in several genes. Consistent with recent proposals, we hypothesized that the association of the interaction of MAOA genotype and maltreatment with aggressive behaviour is further moderated by methylation of a region of interest (ROI) spanning the first exon and partial first intron of MAOA. Method The sample included 117 women and 77 men who completed interviews and questionnaires to report maltreatment and aggressive behaviour towards others and provided saliva samples for DNA extraction. The MAOA-uVNTR polymorphism was genotyped, and methylation of the MAOA ROI was assessed. Results Following adjustment for substance misuse, psychoactive medication use, and in males tobacco use, the highest levels of aggressive behaviour were found among maltreated male carriers of MAOA-S with high levels of exonic methylation. Conclusion Methylation levels within the MAOA ROI further contributed to the interaction of MAOA risk genotypes and maltreatment on aggressive behaviours among men.

    更新日期:2020-01-11
  • Decision urgency invigorates movement in humans
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-09
    David Thura

    Recent work in highly trained monkeys suggests that decision-making and motor control are linked processes whose regulation by urgency allows reward rate optimization. However, such urgency-based mechanism might be species-specific and/or a consequence of practice. Here I show that the unified regulation hypothesis exists in naïve human subjects. Seventeen volunteers performed a reach decision task in which blocks of trials encouraged either risky or conservative choices. Participants performed at least two sessions in which they were indirectly motivated to maximize their reward rate. Results show that subjects’ accuracy criterion decreased over time within each trial, and that decisions were earlier and less accurate in fast than slow blocks, with a larger difference in session #2 compared to session #1. A simple model in which sensory information is combined with a growing urgency signal captured these effects. Crucially, arm and eye movement vigor systematically increased as decision duration increased within blocks and the block-dependent decision policy strongly predicted the kinematics of reaching movements. These results suggest a practice-independent mechanistic link for establishing the unified control of human decision timing and action vigor in order to optimize the rate of reward.

    更新日期:2020-01-09
  • High-Fat diet impairs tactile discrimination memory in the mouse
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-08
    Luke S. Watson; Tyler D. Stone; Dominique Williams; Alexus S. Williams; Catrina Sims-Robinson

    Research on the impact of diet and memory has garnered considerable attention while exploring the link between obesity and cognitive impairment. High-fat diet (HFD) rodent models recapitulate the obesity phenotype and subsequent cognitive impairments. While it is known that high-fat diet is associated with sensory impairment, little attention has been given to the potential role these sensory deficits may play in recognition memory testing, one of the most commonly used cognitive tests. Because mice utilize their facial vibrissae as their primary sensory apparatus, we modified a common recognition test, the novel object recognition task, by replacing objects with sandpaper grits at ground level, herein referred to as the novel tactile recognition task (NTR). First, we tested whisker-manipulated mice in this task to determine its reliance on intact vibrissae. Then, we tested the HFD mouse in the NTR. Finally, to ensure that deficits in the NTR are due to cognitive impairment and not HFD-induced sensory deficiencies, we tested the whisker sensitivity of HFD mice via the corner test. Our results indicate that the NTR is a whisker dependent task, and that HFD mice exhibit tactile recognition memory impairment, not accompanied by whisker sensory deficits.

    更新日期:2020-01-09
  • Administration of diphenyl diselenide (PhSe)2 following repetitive mild traumatic brain injury exacerbates anxiety-like symptomology in a rat model
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-08
    Glenn R Yamakawa; Eric Eyolfson; Himanthri Weerawardhena; Richelle Mychasiuk

    Approximately 10-15% of people that sustain mild traumatic brain injury (mTBI) develop post-concussive syndrome (PCS). PCS is a complex array of symptoms that can result in physical, cognitive and emotional impairments. Following mTBI, there are also complex changes in the oxidative stress system and engagement of the inflammatory system, within the brain. Diphenyl diselenide (PhSe)2 is an organoselenium compound which can play a role in anti-oxidant and anti-inflammatory activities. (PhSe)2 also has many interesting properties including anti-anxiety, anti-depressant and anti-nociception effects. We sought to determine if treatment with (PhSe)2 following repetitive mTBI could have mitigating effects on PCS. To investigate this, we induced mTBI or sham injuries using our lateral impact device in adolescent male and female Sprague Dawley rats and an hour later injected rats with vehicle, 10 mg/kg or 25 mg/kg (PhSe)2 i.p. Next, we conducted a behavioral assessment designed to assess PCS and then euthanized the animals to examine changes in gene expression and telomere length. (PhSe)2 decreased the time to cross the beam, distance travelled and time spent in the centre of the open field, time spent in the open arms of the elevated plus maze, the time investigating both objects in the novel context mismatch and time immobile in the forced swim. This anxiety-like symptomology resolved spontaneously between 10 and 12 days after the third mTBI. We found (PhSe)2 groups showed increased levels of TNF alpha and longer telomeres. We also found higher levels of GPX1 in the injured animals. Our results show that (PhSe)2 exacerbates anxiety-like symptomology in contrast to previous findings.

    更新日期:2020-01-08
  • Dopamine transporter gene expression within the nucleus accumbens plays important role in the acquisition and reinstatement of ethanol-seeking behavior in mice
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-07
    Amine Bahi

    Alcoholism and alcohol use disorders are chronically relapsing conditions which is a major problem in treating alcohol addiction. In a previous study we showed that the dopamine transporter (DAT) is implicated in voluntary intake and preference. However, its role in modulating ethanol-associated contextual memory remains largely unknown. In this study we have investigated the role of DAT in ethanol-induced conditioned place preference (EtOH-CPP) acquisition and reinstatement in adult male C57BL/6 mice. For this purpose, we used both loss- and gain-of-function approaches to test the effects of central DAT manipulation on EtOH-CPP. We developed a lentiviral-mediated gene transfer approach to examine whether DAT knockdown (shDAT) or overexpression in the nucleus accumbens (Nacc) is enough to impair EtOH-CPP acquisition and reinstatement. In the first experiment, results showed that DAT knockdown blocked, whereas DAT overexpression, exacerbated the acquisition of EtOH-CPP. In the second experiment and after the EtOH-CPP expression, the mice were subjected to a 14-day extinction trials before drug-induced EtOH-CPP reinstatement was induced by a priming injection of 1 g/kg EtOH. Results indicated that reinstatement of EtOH-CPP was considerably decreased after accumbal shDAT injection. However, DAT overexpression significantly increased EtOH-CPP reinstatement. Finally, and following DAT mRNA quantification using RT-PCR, Pearson’s correlation showed a strong positive relationship between accumbal DAT mRNA and EtOH-CPP acquisition and reinstatement. These results suggest that DAT expression in the Nacc is involved in the acquisition and retrieval of EtOH contextual memory and that blockade of this transporter can decrease the rewarding properties of EtOH.

    更新日期:2020-01-07
  • MATERNAL DEPRIVATION IMPAIRS MEMORY AND COGNITIVE FLEXIBILITY, EFFECT THAT IS AVOIDED BY ENVIRONMENTAL ENRICHMENT
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-07
    Jefferson Menezes; Ben-Hur Neves; Rithiele Gonçalves; Fernando Benetti; Pâmela Billig Mello-Carpes

    Maternal deprivation (MD) causes cognitive deficits that persist until adulthood. Thereby, the environmental enrichment (EE) is widely used to increase brain plasticity. Here, pregnant female rats were used and their offspring were submitted to neonatal MD from post-natal day 1 to 10; after weaning the rats were submitted to EE. MD caused deficits on short and long-term aversive and recognition memory and on cognitive flexibility tested on reversed Morris Water Maze test. MD also promoted the decrease of hippocampal Brain-Derived Neurotropic Factor (BDNF) protein expression. The EE was able to protect against the cognitive deficits, avoiding the memory and the cognitive flexibility disrupting, and normalizing hippocampal BDNF expression of rats submitted to MD. These data confirms that MD promotes long-life memory deficits and demonstrates that MD causes cognitive flexibility disruption; the mechanisms seem involve the decrease of BDNF. We also demonstrate that EE, which improves BNDF, is able to avoid memory deficits and cognitive flexibility disrupts.

    更新日期:2020-01-07
  • Defensive behaviors and brain regional activation changes in rats confronting a snake
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-07
    Joyce Mendes-Gomes; Simone Cristina Motta; Ricardo Passoni Bindi; Amanda Ribeiro de Oliveira; Farhad Ullah; Marcus Vinicius C. Baldo; Norberto Cysne Coimbra; Newton Sabino Canteras; D. Caroline Blanchard

    In the present study, we examined behavioral and brain regional activation changes of rats). to a nonmammalian predator, a wild rattler snake (Crotalus durissus terrificus). Accordingly, during snake threat, rat subjects showed a striking and highly significant behavioral response of freezing, stretch attend, and, especially, spatial avoidance of this threat. The brain regional activation patterns for these rats were in broad outline similar to those of rats encountering other predator threats, showing Fos activation of sites in the amygdala, hypothalamus, and periaqueductal gray matter. In the amygdala, only the lateral nucleus showed significant activation, although the medial nucleus, highly responsive to olfaction, also showed higher activation. Importantly, the hypothalamus, in particular, was somewhat different, with significant Fos increases in the anterior and central parts of the ventromedial hypothalamic nucleus (VMH), in contrast to patterns of enhanced Fos expression in the dorsomedial VMH to cat predators, and in the ventrolateral VMH to an attacking conspecific. In addition, the juxtodorsalmedial region of the lateral hypothalamus showed enhanced Fos activation, where inputs from the septo-hippocampal system may suggest the potential involvement of hippocampal boundary cells in the very strong spatial avoidance of the snake and the area it occupied. Notably, these two hypothalamic paths appear to merge into the dorsomedial part of the dorsal premammillary nucleus and dorsomedial and lateral parts of the periaqueductal gray, all of which present significant increases in Fos expression and are likely to be critical for the expression of defensive behaviors in responses to the snake threat.

    更新日期:2020-01-07
  • Sexually Dimorphic Behavioral and Neural Responses to a Predator Scent
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-07
    Jennifer A. Francesconi; Cathleen Macaroy; Shreeya Sawant; Haleigh Hamrick; Sameerah Wahab; Ilana Klein; John P. McGann

    Male and female C57BL/6 J mice were tested on the predator odor response task, where they needed to cross through a chamber of scented bedding to reach a sucrose reward. Following the behavioral testing, mouse brains were immunohistochemically labeled for expression of the immediate early gene c-fos. In the presence of the novel odorant methyl valerate (MV), both males and females exhibited increased exploration behaviors and delayed rewards compared to control bedding. However, in the presence of the predator odor phenylethylamine (PEA), males exhibited increased exploration that strongly resembled their behavior in MV (a non-predator odor) while females behaved very similarly to the clean bedding controls, quickly traversing the chamber to achieve the reward. Expression of c-fos exhibited significant sex by odor condition interactions overall across brain regions and in the anterior piriform cortex, cingulate cortex, and dorsomedial hypothalamus specifically. In all three regions we observed the general pattern that PEA exposure evoked elevated c-fos expression in females but suppressed c-fos expression in males. Taken together these data suggest that males and females may adopt different behavioral strategies in the presence of predator threat.

    更新日期:2020-01-07
  • Functional Neurogenesis Over the Years
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-07
    Jason S. Snyder; Michael R. Drew

    There has been interest in the function of adult neurogenesis since its discovery, by Joseph Altman, nearly 60 years ago. While controversy curtailed follow up studies, in the 1990s a second wave of research validated many of Altman’s original claims and revealed that factors such as stress and environmental stimulation altered the production of new neurons in the hippocampus. However, only with the advent of tools for manipulating neurogenesis did it become possible to perform causal tests of the function of newborn neurons. Here, we identify approximately 100 studies in which adult neurogenesis was manipulated to study its function. A majority of these studies demonstrate functions for adult neurogenesis in classic hippocampal behaviors such as context learning and spatial memory, as well as emotional behaviors related to stress, anxiety and depression. However, a closer look reveals a number of other, arguably understudied, functions in decision making, temporal association memory, and addiction. In this special issue, we present 16 new studies and review articles that continue to address and clarify the function of adult neurogenesis in behaviors as diverse as memory formation and consolidation, pattern separation and discrimination behaviors, addiction, and attention. Reviews of stem cell dynamics and regenerative properties provide insights into the mechanisms by which neurogenesis may be controlled to offset age- and disease-related brain injury. Finally, translation-oriented reviews identify next steps for minimizing the gap between discoveries made in animals and applications for human health. The articles in this issue synthesize and extend what we have learned in the last half century of functional neurogenesis research and identify themes that will define its future.

    更新日期:2020-01-07
  • Frontal volume as a potential source of the comorbidity between attention-deficit/hyperactivity disorder and reading disorders
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-07
    Michelle Y. Kibby; Sarah M. Dyer; Sylvia E. Lee; Maria Stacy

    Prefrontal volume reductions commonly are demonstrated in ADHD, but the literature examining prefrontal volume in reading disorders (RD) is scant despite their also having executive functioning (EF) deficits. Furthermore, only a few anatomical studies have examined the frontal lobes in comorbid RD/ADHD, though they have EF deficits similar to RD and ADHD. Hence, we examined frontal gyri volume in children with RD, ADHD, RD/ADHD and controls, as well as their relationship to EF for gyri found to differ between groups. We found right inferior frontal (RIF) volume was smaller in ADHD, and smaller volume was related to worse behavioral regulation. Left superior frontal (LSF) volume was larger in RD than ADHD, and its size was negatively related to basic reading ability. Left middle frontal (LMF) volume was largest in RD/ADHD overall. Further, its volume was not related to basic reading nor behavioral regulation but was related to worse attentional control, suggesting some specificity in its EF relationship. When examining hypotheses on the etiology of RD/ADHD, RD/ADHD was commensurate with ADHD in RIF volume and both RD and ADHD in LSF volume (being midway between the groups), consistent with the common etiology hypothesis. Nevertheless, they also had an additional gyrus affected: LMF, consistent with the cognitive subtype hypothesis in its specificity to RD/ADHD. The few other frontal aMRI studies on RD/ADHD supported both hypotheses as well. Given this, future research should continue to focus on frontal morphology in its endeavors to find neurobiological contributors to the comorbidity between RD and ADHD.

    更新日期:2020-01-07
  • Adult neurogenesis, human after all (again): classic, optimized, and future approaches
    Behav. Brain Res. (IF 2.770) Pub Date : 2019-12-30
    Paul J. Lucassen; Carlos P. Fitzsimons; Evgenia Salta; Mirjana Maletic-Savatic

    In this perspective article, we reflect on the recent debate about the existence of human neurogenesis and discuss direct, and also indirect, support for the ongoing formation, and functional relevance, of new neurons in the adult and aged human hippocampus. To explain the discrepancies between several prominently published human studies, we discuss critical methodological aspects and highlight the importance of optimal tissue preservation and processing for histological examination. We further discuss novel approaches, like single-cell/nucleus sequencing and magnetic resonance spectroscopy, that will help advance the study of human neurogenesis to its fullest potential – understanding its contribution to human hippocampal functions and related disorders like depression and dementia.

    更新日期:2019-12-31
  • Sex Differences in Cognitive Performance and Alcohol Consumption in High Alcohol-Drinking (HAD-1) Rats
    Behav. Brain Res. (IF 2.770) Pub Date : 2019-12-28
    N. Mittal; SM Fleming; A Martinez; N Thakore; RL Bell; WT Maddox; T Schallert; CL Duvauchelle

    Excessive alcohol (ethanol) consumption negatively impacts social, emotional, as well as cognitive function and well-being. Thus, identifying behavioral and/or biological predictors of excessive ethanol consumption is important for developing prevention and treatment strategies against alcohol use disorders (AUDs). Sex differences in alcohol consumption patterns are observed in humans, primates, and rodents. Selectively bred high alcohol-drinking rat lines, such as the “HAD-1” lines are recognized animal models of alcoholism. The present work examined sex differences in alcohol consumption, object recognition, and exploratory behavior in male and female HAD-1 rats. Naïve male and female HAD-1 rats were tested in an object recognition test (ORT) prior to a chronic 24 h intermittent ethanol access procedure for five weeks. Object recognition parameters measured included exploratory behavior, object investigation, and time spent near objects. During the initial training trial, rearing, active object investigation and amount of time spent in the object-containing section was significantly greater in female HAD-1 rats compared to their male counterparts. During the subsequent testing trial, time spent in the object-containing section was greater in female, compared to male, rats; but active object investigation and rearing did not statistically differ between females and males. In addition, female HAD-1 rats consumed significantly more ethanol than their male counterparts, replicating previous findings. Moreover, across all animals there was a significant positive correlation between exploratory behavior in ORT and ethanol consumption level. These results indicate there are significant sex differences in cognitive performance and alcohol consumption in HAD-1 rats, which suggests<-- --> neurobiological differences as well.

    更新日期:2019-12-29
  • Improved survival and overt “dystonic” symptoms in a torsinA hypofunction mouse model
    Behav. Brain Res. (IF 2.770) Pub Date : 2019-12-28
    Fumiaki Yokoi; Fangfang Jiang; Kelly Dexter; Bryan Salvato; Yuqing Li

    DYT1 dystonia is an inherited movement disorder without obvious neurodegeneration. Multiple mutant mouse models exhibit motor deficits without overt “dystonic” symptoms and neurodegeneration. However, some mouse models do. Among the later models, the N-CKO mouse model, which has a heterozygous Tor1a/Dyt1 knockout (KO) in one allele and Nestin-cre-mediated conditional KO in the other, exhibits a severe lack of weight gain, neurodegeneration, overt “dystonic” symptoms, such as overt leg extension, weak walking, twisted hindpaw and stiff hindlimb, and complete infantile lethality. However, it is not clear if the overt dystonic symptoms were caused by the neurodegeneration in the dying N-CKO mice. Here, the effects of improved maternal care and nutrition during early life on the symptoms in N-CKO mice were analyzed by culling the litter and putting wet food to examine whether the overt dystonic symptoms and severe lack of weight gain are caused by malnutrition-related neurodegeneration. Although the N-CKO mice in this study replicated the severe lack of weight gain and overt “dystonic” symptoms during the lactation period regardless of culling at postnatal day zero or later, there was no significant difference in the brain astrocytes and apoptosis between the N-CKO and control mice. Moreover, more than half of the N-CKO mice with culling survived past the lactation period. The surviving adult N-CKO mice did not display overt “dystonic” symptoms, whereas they still showed small body weight. The results suggest that the overt “dystonic” symptoms in the N-CKO mice were independent of prominent neurodegeneration, which negates the role of neurodegeneration in the pathogenesis of DYT1 dystonia.

    更新日期:2019-12-29
  • Differential effects of prior stress on conditioned inhibition of fear and fear extinction
    Behav. Brain Res. (IF 2.770) Pub Date : 2019-12-28
    Ellen P. Woon; Tara A. Seibert; Phillip J. Urbanczyk; Ka H. Ng; Susan Sangha

    Resistant and generalized fear are hallmark symptoms of Post-Traumatic Stress Disorder (PTSD). Given PTSD is highly comorbid with addiction disorders indicates a maladaptive interaction between fear and reward circuits. To investigate learning processes underlying fear, reward and safety, we trained male rats to discriminate among a fear cue paired with footshock, a reward cue paired with sucrose and an explicit safety cue co-occurring with the fear cue in which no footshocks were delivered. In an attempt to emulate aspects of PTSD, we pre-exposed male rats to a stressor (15 unsignaled footshocks) before training them to fear, reward and safety cues, and subsequent fear and reward extinction. Prior stress did not produce any significant impairments on conditioned inhibition to a safety cue compared to non-stressed controls. However, in subsequent fear extinction, prior stress profoundly impaired fear reduction to an extinguished fear cue. Prior stress also significantly reduced reward seeking to a reward-associated cue throughout training. Together, our data show that prior stress did not affect conditioned inhibition of fear to the same extent as impairing fear extinction. These results have interesting implications on how safety circuits are organized and impacted by stress, leading to possibly new avenues of research on mechanisms of stress disorders, such as PTSD.

    更新日期:2019-12-29
  • Emotional memory impairment produced by binge drinking in mice is counteracted by the anti-inflammatory indomethacin
    Behav. Brain Res. (IF 2.770) Pub Date : 2019-12-28
    Santiago Monleón; Aranzazu Duque; Concepción Vinader-Caerols

    The Binge Drinking (BD) pattern of alcohol consumption, prevalent in adolescents and young adults, has been associated with memory impairment. In addition, evidence shows that alcohol abuse causes neuroinflammation, which may contribute to the brain damage produced by alcohol and explain its cognitive consequences. In this study, we evaluated the effectiveness of the anti-inflammatory indomethacin in counteracting the memory impairment produced by alcohol (ethanol) in adolescent mice of both sexes. Animals were randomly assigned to one of four groups for each sex: SS (saline + saline), SA (saline + alcohol), SI (saline + indomethacin) and AI (alcohol + indomethacin). They were injected acutely (Experiment 1) or chronically intermittent (Experiment 2) with saline, ethanol (3 g/kg) and indomethacin (10 mg/kg). All subjects were evaluated in an inhibitory avoidance task 96 h after treatment. With acute administration, SA groups showed significantly lower Test latencies than SS groups, while AI groups had similar latencies to controls. The chronic-intermittent administration of alcohol, an animal model of BD, produced significant emotional memory impairment -blocking learning in males- which was counteracted by indomethacin, as the AI groups had similar latencies to the SS groups. No significant differences were observed in locomotor activity or analgesia. In conclusion, alcohol BD (one or several episodes) impairs emotional memory in mice. This impairment is not secondary to the effects of alcohol BD on locomotor activity or pain sensitivity, and it is counteracted by indomethacin. Therefore, the memory impairment produced by alcohol BD seems to be mediated, in part, by neuroinflammatory processes. These findings open a window for new treatments for alcohol use disorders.

    更新日期:2019-12-29
  • Object and food novelty induce distinct patterns of c-fos immunoreactivity in amygdala and striatum in domestic male chicks (Gallus gallus domesticus)
    Behav. Brain Res. (IF 2.770) Pub Date : 2019-12-26
    Emilie C. Perez; Maryse Meurisse; Lucile Hervé; Marion Georgelin; Paul Constantin; Fabien Cornilleau; Scott A. Love; Frédéric Lévy; Ludovic Calandreau; Aline Bertin

    Avoidance of novelty, termed neophobia, protects animals from potential dangers but can also impair their adaptation to novel environments or food resources. This behaviour is particularly well described in birds but the neurobiological correlates remain unexplored. Here, we measured neuronal activity in the amygdala and the striatum, two brain regions believed to be involved in novelty detection, by labelling the early gene c-fos following chicks exposure to a novel food (NF), a novel object (NO) or a familiar food (FF). NF and NO chicks showed significantly longer latencies to touch the food, less time eating and emitted more fear-vocalizations than control chicks. Latency to touch the food was also longer for NO than for NF chicks. Significantly higher densities of c-fos positive cells were present in all the nuclei of the arcopallium/amygdala of NF and NO chicks compared to FF chicks. Also, NO chicks showed higher positive cell densities than NF chicks in the posterior amygdaloid, the intermediate and the medial arcopallium. Exposure to novel food or object induced a similar increase in c-fos expression in the nucleus accumbens and the medial striatum. Our data provide evidence activation of the arcopallium/amygdala is specific of the type of novelty. The activation of striatum may be more related to novelty seeking.

    更新日期:2019-12-27
  • 更新日期:2019-12-25
  • Effects of perirhinal cortex and hippocampal lesions on rats’ performance on two object-recognition tasks
    Behav. Brain Res. (IF 2.770) Pub Date : 2019-12-23
    Emily Cole; Joelle Ziadé; Amanda Simundic; Dave G. Mumby

    The effects of hippocampal (HPC) damage on rats’ novel object preference (NOP) performance have been rather consistent, in that HPC lesions do not disrupt novelty preferences on the test. Conversely, there have been inconsistent findings regarding the effects of perirhinal cortex (PRh) lesions on rats’ novel-object preferences. Given the concerns that have been raised regarding the internal validity of the NOP test, viz. that the magnitude of the novel-object preference does not necessarily reflect the strength in memory for an object, it could explain the discrepant findings. The goal of the present experiment was to examine the effects of PRh and HPC lesions on rats’ object-recognition memory using a new modified delayed nonmatching-to-sample (mDNMS) task, as it circumvents the interpretational problems associated with the NOP test. Rats received PRh, HPC, or Sham lesions and were trained on the mDNMS task using a short delay (∼30 s). Both PRh and HPC rats acquired the task at the same rate as Sham rats, and reached a similar level of accuracy, indicating intact object-recognition. Thereafter, rats were tested on the NOP test using a 180-s delay. Rats with HPC lesions exhibited significant novel-object preferences, however, both the PRh and Sham rats failed to show a novelty preference. The discrepancy in both the PRh and Sham rats’ performance on the mDNMS task and NOP test raises concerns regarding the internal validity of the NOP test, in that the magnitude of a rat’s novel-object preference does not accurately reflect the persistence or accuracy of a rat’s memory for the sample object.

    更新日期:2019-12-23
  • Indices of dentate gyrus neurogenesis are unaffected immediately after or following withdrawal from morphine self-administration compared to saline self-administering control male rats
    Behav. Brain Res. (IF 2.770) Pub Date : 2019-12-20
    Sarah E. Bulin; Steven J. Simmons; Devon R. Richardson; Sarah E. Latchney; Hannah M. Deutsch; Sanghee Yun; Amelia J. Eisch

    Opiates – including morphine – are powerful analgesics with high abuse potential. In rodents, chronic opiate exposure or self-administration negatively impacts hippocampal-dependent function, an effect perhaps due in part to the well-documented opiate-induced inhibition of dentate gyrus (DG) precursor proliferation and neurogenesis. Recently, however, intravenous (i.v.) morphine self-administration (MSA) was reported to enhance the survival of new rat DG neurons. To reconcile these disparate results, we used rat i.v. MSA to assess 1) whether a slightly-higher dose MSA paradigm also increases new DG neuron survival; 2) how MSA influences cells in different stages of DG neurogenesis, particularly maturation and survival; and 3) if MSA-induced changes in DG neurogenesis persist through a period of abstinence. To label basal levels of proliferation, rats received the S-phase marker bromodeoxyuridine (BrdU, i.p.) 24 -hs prior to 21 days (D) of i.v. MSA or saline self-administration (SSA). Either immediately after SA (0-D) or after 4 weeks in the home cage (28-D withdrawal), stereology was used to quantify DG proliferating precursors (or cells in cell cycle; Ki67+ cells), neuroblast/immature neurons (DCX + cells), and surviving DG granule cells (BrdU + cells). Analysis revealed the number of DG cells immunopositive for these neurogenesis-relevant markers was similar between MSA and SSA rats at the 0-D or 28-D timepoints. These negative data highlight the impact experimental parameters, timepoint selection, and quantification approach have on neurogenesis results, and are discussed in the context of the large literature showing the negative impact of opiates on DG neurogenesis.

    更新日期:2019-12-20
  • Wheel Running for 26 Weeks is Associated with Sustained Vascular Plasticity in the Rat Motor Cortex
    Behav. Brain Res. (IF 2.770) Pub Date : 2019-12-20
    Morgan E. Stevenson; Jacob J.M. Kay; Farid Atry; Alexander T. Wickstrom; Josephine R. Krueger; Ramin E. Pashaie; Rodney A. Swain

    Vascular pathologies represent the leading causes of mortality worldwide. The nervous system has evolved mechanisms to compensate for the cerebral hypoxia caused by many of these conditions. Vessel dilation and growth of new vessels are two prominent responses to hypoxia, both of which play a critical role in maintaining cerebral homeostasis. One way to facilitate cerebrovascular plasticity, and develop neuroprotection against vascular pathologies, is through aerobic exercise. The present study explored the long-term consequences of aerobic exercise on vascular structure and function in the motor cortex. Rats were assigned to a sedentary condition or were provided access to running wheels for 26 weeks. Rats were then anesthetized, and angiograms were captured using spectral domain optical coherence tomography (SD-OCT) to explore cerebrovascular reactivity in response to altered oxygen and carbon dioxide status. Following this procedure, all rats were euthanized, and unbiased stereological quantification of blood vessel density was collected from sections of the primary motor cortex infused with India ink. Results demonstrated that chronic exercise increased capillary and arteriole surface area densities and enhanced arteriole reactivity in response to hypercapnia-hypoxia, as displayed by increased vasodilation within the motor cortex of exercised animals.

    更新日期:2019-12-20
  • The effects of multiple early life stressors on adolescent alcohol consumption
    Behav. Brain Res. (IF 2.770) Pub Date : 2019-12-20
    Shannon M. Thompson; Amber N. Simmons; Matthew S. McMurray

    Alcohol use disorder is pervasive and effects the health of millions. Identifying factors such as early life stress that contribute to the development of alcohol use disorder is therefore critical, especially those that contribute to adolescent drinking, a strong predictor of AUD development. The majority of prior studies have examined early life effects on adult drinking, but have not studied intake during adolescence, and no prior studies have examined how the effects of multiple stressors may be additive. Therefore, this study determined if experiencing individual or multiple stressors increases adolescent alcohol intake. Male Long Evans rats underwent either early or late maternal separation (postnatal day 2-9 or 13-20), early adolescent social defeat (PND 30-40), both, or neither. All rats were then given two-hour access to alcohol, and voluntary intake assessed daily in late adolescence (PND 41-51). In adulthood, sensitivity to alcohol’s sedative effects was assessed using loss and regain of righting reflex tests. Results indicate that experiencing maternal separation (at either time point) or social defeat increased adolescent alcohol consumption, but experiencing the combined stressors did not, and that no stressor significantly affected body weight during adolescence or loss and regain of righting reflex in adulthood. Overall, this pattern of effects suggests that experiencing any individual early life stressor may increase adolescent alcohol intake, in agreement with prior literature, but that the combined effects of multiple early life stressors may be more complicated.

    更新日期:2019-12-20
  • Alarm cue-mediated response and learning in zebrafish larvae
    Behav. Brain Res. (IF 2.770) Pub Date : 2019-12-20
    Tyrone Lucon-Xiccato; Giuseppe Di Mauro; Angelo Bisazza; Cristiano Bertolucci

    We investigated the behavioural and learning response of zebrafish larvae to chemicals released by injured conspecifics (the alarm cue). Many aquatic vertebrates and invertebrates exhibit an innate antipredator response to alarm cues because in nature, they reliably indicate the presence of predators. Likewise, when an individual simultaneously perceives a novel odour and alarm cue, it learns to recognise the novel odour as a predator odour. Alarm cue-mediated behavioural response and learning have been reported in some fish and amphibians during early ontogeny, but in zebrafish, they have been described only for adults. In this study, we demonstrated that zebrafish at 12 and 24 days post fertilization exhibited reduced activity when exposed to alarm cue obtained by homogenised larvae of the same age, with this response being greater for the older zebrafish. In addition, we showed that 24-dpf zebrafish conditioned with alarm cue plus a novel odour learned to recognise the novel odour as a threat and responded to it with antipredator behaviour. The innate behavioural response and the learned response after conditioning may be used to develop paradigms with which to study anxiety, fear, stress, learning and memory in zebrafish larvae.

    更新日期:2019-12-20
  • Combined use of alcohol and cigarette increases locomotion and glutamate levels in the cerebrospinal fluid without changes on GABAA or NMDA receptor subunit mRNA expression in the hippocampus of rats
    Behav. Brain Res. (IF 2.770) Pub Date : 2019-12-19
    Solange Bandiera; Felipe Borges Almeida; Alana Witt Hansen; Rianne Remus Pulcinelli; Greice Caletti; Leonardo Fernandes de Paula; Mauricio Schüler Nin; Fernanda Urruth Fontella; Roberto Farina Almeida; Helena Maria Tannhauser Barros; Rosane Gomez

    Interactions on neurotransmitter systems in the reward pathways may explain the high frequency of combined use of alcohol and cigarettes in humans. In this study, we evaluated some behavioral and neurochemical changes promoted by chronic exposure to alcohol and cigarette smoke in rats. Adult rats were administered with 2 g/kg alcohol (v.o.) or/and inhaled the smoke from 6 cigarettes, twice/day, for 30 days. Behavioral tests were performed 3 h after the alcohol administration and 1 h after the last exposure to cigarette smoke in the morning. Cerebrospinal fluid was collected for glutamate determination and the hippocampus was dissected for GABAA and NMDA receptor subunits mRNA expression determination. Results showed that the combined use of alcohol and cigarette smoke (ALTB) in rats increased the locomotor activity and all interventions decreased anxiety-like behaviors. Despite being on a short-term withdrawal, the cigarette smoke exposure decreased the percentage of open arm entries in the elevated plus maze test, which was prevented by combined use with alcohol. Even though GABAA and glutamate receptor subunits expression did not change in the hippocampus, glutamate levels were significantly higher in the cerebrospinal fluid from ALTB rats. Therefore, we showed that the combined use of alcohol and cigarette maintained a psychostimulant effect after a short-term withdrawal that was associated with the elevated glutamatergic activity. The combined use also prevented anxiety-like signs in cigarette smoke exposure rats, decreasing an adverse effect caused by nicotine withdrawal. These results could explain, in part, the elevated frequency of combined use of these two drugs of abuse in humans.

    更新日期:2019-12-19
  • Treadmill Exercise Improves LPS-Induced Memory Impairments via Endocannabinoid Receptors and Cyclooxygenase Enzymes
    Behav. Brain Res. (IF 2.770) Pub Date : 2019-12-19
    Moosavi Sohroforouzani Azam; Shakeryan Saeed; Ghanbarzadeh Mohsen; Alaei Hojjatallah

    Endocannabinoid system and cyclooxygenase enzymes are implicated in neuroinflammation-induced cognitive impairment. It is believed that non-pharmacological treatments such as physical exercise affect neural systems that control behavioral responses. This research examined the effects of treadmill aerobic exercise on the expression of cannabinoid receptors and cyclooxygenases against LPS-induced cognitive disorders in the hippocampus tissue of rats. For this purpose, rats received intraperitoneal injection of 0.25 mg/kg LPS or saline for 9 continuous days before exercise training. They again received a single i.p. injection with 0.5 mg/kg LPS or saline on days 20 and 41 after the beginning of exercise. The exercise groups were forced to run on a motorized treadmill 5 days per week for 8 weeks. After the last exercise training session, the water maze test was conducted to measure cognitive function. Finally, the hippocampus tissue samples of rats were removed and used to determine the levels of gene expression using the Real-Time PCR method. Data showed that the LPS-treated rats had longer escape distance and longer escape latency to reach the hidden platform and they spent less time than the other groups in the target quadrant, but exercise training improved them in the LPS + Exe (LPS + exercise) group. Exercise increased the expression of CB1 receptor in the Sal + Exe (saline + exercise) group and reduced the expression of CB2 receptor, COX-2 and mPGES-1 in the LPS + Exe group compared to the Sal + LPS group. The findings indicate that treadmill exercise may be beneficial for improvement of cognitive function by modulating the neuroinflammatory processes.

    更新日期:2019-12-19
  • THE INFLUENCE OF DOPAMINERGIC POLYMORPHISMS ON SELECTIVE STOPPING
    Behav. Brain Res. (IF 2.770) Pub Date : 2019-12-19
    I. Rincón-Pérez; V. Echeverry-Alzate; A.J. Sánchez-Carmona; K.M. Bühler; J.A. Hinojosa; J.A. López-Moreno; J. Albert

    Although the genetic influence on global stopping has been extensively investigated, little is known about the genetic contribution to other more complex forms of inhibitory control such as selective stopping. The selectivity of inhibitory control can be assessed by using the stimulus-selective stop-signal task. Notably, recent behavioural and neural evidence indicates that individuals can adopt selective but also non-selective stopping strategies to solve it. This study aimed to investigate for the first time the influence of two relevant dopaminergic polymorphisms (in COMT and DRD2 genes) on stimulus-selective stopping in a sample of 529 adults. Results showed that although none of these polymorphisms (neither individually nor in combination) modulate the latency of the stop process in each strategy (the stop-signal reaction time), the choice of strategy was influenced by their interaction. These results suggest that dopaminergic polymorphisms might influence strategy adoption in selective stopping paradigms, which constitutes a novel finding.

    更新日期:2019-12-19
  • Short-term selection for high and low ethanol intake during adolescence exerts lingering effects in stress-induced ethanol drinking and yields an anxiety-prone phenotype
    Behav. Brain Res. (IF 2.770) Pub Date : 2019-12-19
    Macarena Soledad Fernández; Fabio Bellia; Ana Ferreyra; Florencia Chiner; Ana María Jiménez García; Claudio D’Addario; Ricardo Marcos Pautassi

    Ethanol use is widespread in adolescents, yet only some transition to problematic drinking. It is important to understand why the risk for problematic drinking varies across sub-groups of adolescents. This study reports a short-term selection program to generate Wistar rat lines (high and low adolescent ethanol drinking, ADHI and ADLO lines, respectively) that significantly differ in ethanol drinking at adolescence. The S0 generation and filial generations 1 (S1), S2, and S3 of ADHI and ADLO offspring were tested for basal or stress-induced ethanol intake at adulthood, or for shelter-seeking and risk-taking in the multivariate concentric square field test (MSCF). The study generated lines with significant differences in free-choice ethanol drinking at adolescence. The effects of the selection were observed at adulthood, beyond the stage in which the selection was conducted: S1-ADHI but not S1-ADLO adult male rats exhibited stress-induced drinking. These effects were associated with significant alterations in shelter-seeking and risk-taking behaviors. ADHI rats spent significantly less time in areas of the MSCF whose exploration entails risk-taking and significantly more time in dark, sheltered areas. Some of these effects were normalized by the administration of 0.5 g/kg ethanol. There were no line differences in ethanol-induced latency to lose the righting reflex or sleep time. These findings indicate that genetic risk of enhanced ethanol intake at adolescence is still present at adulthood, long after the developmental window when the selective breeding occurred. Exposure to stress at adulthood triggers the vulnerability associated with this genetic risk, an effect associated with enhanced anxiety.

    更新日期:2019-12-19
  • Changes in brain activation related to visuo-spatial memory after real-time fMRI neurofeedback training in healthy elderly and Alzheimer's disease
    Behav. Brain Res. (IF 2.770) Pub Date : 2019-12-18
    Christian Hohenfeld; Hanna Kuhn; Christine Müller; Nils Nellessen; Simon Ketteler; Armin Heinecke; Rainer Goebel; N. Jon Shah; Jörg B. Schulz; Martina Reske; Kathrin Reetz

    Cognitive decline is a symptom of healthy ageing and Alzheimer's disease. We examined the effect of real-time fMRI based neurofeedback training on visuo-spatial memory and its associated neuronal response. Twelve healthy subjects and nine patients of prodromal Alzheimer's disease were included. The examination spanned five days (T1–T5): T1 contained a neuropsychological pre-test, the encoding of an itinerary and a fMRI-based task related that itinerary. T2–T4 hosted the real-time fMRI neurofeedback training of the parahippocampal gyrus and on T5 a post-test session including encoding of another itinerary and a subsequent fMRI-based task were done. Scores from neuropsychological tests, brain activation and task performance during the fMRI-paradigm were compared between pre and post-test as well as between healthy controls and patients. Behavioural performance in the fMRI-task remained unchanged, while cognitive testing showed improvements in visuo-spatial memory performance. Both groups displayed task-relevant brain activation, which decreased in the right precentral gyrus and left occipital lobe from pre to post-test in controls, but increased in the right occipital lobe, middle frontal gyrus and left frontal lobe in the patient group. While results suggest that the training has affected brain activation differently between controls and patients, there are no pointers towards a behavioural manifestation of these changes. Future research is required on the effects that can be induced using real-time fMRI based neurofeedback training and the required training duration to elicit broad and lasting effects.

    更新日期:2019-12-19
  • PLACE PREFERENCES INDUCED BY ELECTRICAL STIMULATION OF THE EXTERNAL LATERAL PARABRACHIAL SUBNUCLEUS IN A SEQUENTIAL LEARNING TASK
    Behav. Brain Res. (IF 2.770) Pub Date : 2019-12-18
    María M. Hurtado; Raquel García; Amadeo Puerto

    It is known that electrical stimulation of the external lateral parabrachial nucleus (NLPBe) can sustain concurrent taste and place learning. Place preferences can be learned through different procedures. Previous studies demonstrated that electrical stimulation of the PBNLe can generate aversive and preference place learning using concurrent procedures. In the concurrent procedure, the animals can move freely in the maze, and intracranial electrical stimulation is associated with their voluntary stay in one of the two maze compartments. However, the rewarding properties of most stimuli, whether natural or drugs of abuse, have usually been investigated using the sequential procedure, in which animals are confined while receiving the unconditioned stimulus and then undergo a choice test without stimulation in a later phase. This study examined whether this stimulation can sustain place preference learning in sequential tasks. Results demonstrated that place preferences can also be induced by the electrical stimulation of the NLBe using sequential procedures. These findings suggest that the NLPBe may form part of a brain reward axis that shares certain characteristics with those observed in the processing of natural rewarding agents and especially of drugs of abuse.

    更新日期:2019-12-18
  • Hyperactive movement behaviour of athletes with post-concussion symptoms
    Behav. Brain Res. (IF 2.770) Pub Date : 2019-12-17
    Ingo Helmich; Nicola Nussbaum; Hedda Lausberg

    Objective Observations of hyperactive (/restless, agitated) behaviour as a consequence of mild traumatic brain injuries (mTBI) in sports are inconclusive as reduced or slowed movement behaviour is also commonly described post-concussion. This might be grounded in the fact that the movement behaviour of athletes has not been systematically investigated during standardized settings and with objective methods of nonverbal movement analysis. Thus, we investigate whether symptoms after mTBI in sports are characterized by a hyper- or hypoactive movement behaviour experimentally. Methods Three matched groups of 40 athletes were investigated: 14 symptomatic and 14 asymptomatic athletes with a mTBI; and 12 non-concussed athletes. Four certified raters analysed with a standard analysis system for nonverbal behaviour each athlete’s hand movement activity, hand movement contacts, and resting positions that were displayed during a videotaped standardized anamnesis protocol. Results Symptomatic athletes spend significantly more time with act apart hand movements and less time with closed rest positions when compared to non-concussed athletes. Post-concussion symptom (PCS) scores positively correlate with act apart hand movements. A linear regression analysis revealed that act apart hand movements significantly predict the PCS score. Conclusions Athletes with increased symptoms after mTBI move their hands in a hyperactive and restless manner. Increased act apart hand movements, i.e., when both hands move simultaneously without touching each other, indicate a motoric destabilization in symptomatic athletes’ behaviour that might be related to impaired inhibitory motor control systems. Future diagnoses should concern the systematic analysis of the nonverbal movement behaviour as a potential behavioural marker of symptoms after mTBI.

    更新日期:2019-12-18
  • Antidepressant-like Effects of β-caryophyllene on Restraint Plus Stress-induced Depression
    Behav. Brain Res. (IF 2.770) Pub Date : 2019-12-17
    Eun-Sang Hwang; Hyun-Bum Kim; Seok Lee; Min-Jeong Kim; Kwan-Joong Kim; Gaeul Han; Se-Young Han; Eun-A Lee; Jeong-Hee Yoon; Dae-Ok Kim; Sungho Maeng; Ji-Ho Park

    Chronic stress is depressogenic by altering neurotrophic and neuroinflammatory environments of the organism. The endocannabinoid system controls cognitive and emotional responses related with stress through the interaction with endocannabinoid receptors. β-Caryophyllene (BCP) is a CB2 agonist that exhibited anti-inflammatory, analgesic effects but minimal psychoactive effects. To test if BCP exhibits antidepressant-like action, animals were chronically restrained with additional stressors for 28 days, and BCP (25, 50, 100 mg/kg) was intraperitoneally injected once a day during the stress inflicting period. Then despair related behaviors and hippocampal expression of neurotrophic, inflammatory and cannabinoid receptor levels were measured. To test the effect of BCP on long-term depression, field potentials were measured during the application of lipopolysaccharide and low frequency stimulation. In the tail suspension test and forced swim test, chronic stress-induced despair behaviors were reduced by BCP. Also BCP improved the stress-related changes in the hippocampal expression of COX-2, BDNF, and CB2 receptor expression. In organotypic hippocampal slices, BCP reduced the lipopolysaccharide-induced intensification of the long-term depression. In conclusion, BCP improved chronic stress related behavioral and biochemical changes. These results suggest that BCP may be effective in treating depression and stress related mental illnesses.

    更新日期:2019-12-18
  • Seasonal changes of perineuronal nets and song learning in adult canaries (Serinus canaria)
    Behav. Brain Res. (IF 2.770) Pub Date : 2019-12-16
    Gilles Cornez; Clémentine Collignon; Wendt Müller; Gregory F. Ball; Charlotte A. Cornil; Jacques Balthazart

    Songbirds learn their song during a sensitive period of development associated with enhanced neural plasticity. In addition, in open-ended learners such as canaries, a sensitive period for sensorimotor vocal learning reopens each year in the fall and leads to song modifications between successive breeding seasons. The variability observed in song production across seasons in adult canaries correlates with seasonal fluctuations of testosterone concentrations and with morphological changes in nuclei of the song control system (SCS). The sensitive periods for song learning during ontogeny and then again in adulthood could be controlled by the development of perineuronal nets (PNN) around parvalbumin-expressing interneurones (PV) which limits learning-induced neuroplasticity. However, this relationship has never been investigated in the context of adult vocal learning in adult songbirds. Here we explored PNN and PV expression in the SCS of adult male Fife Fancy canaries in relation to the seasonal variations of their singing behaviour. We found a clear pattern of seasonal variation in testosterone concentrations and song production. Furthermore, PNN expression was significantly higher in two specific song control nuclei, the robust nucleus of the arcopallium (RA) and the Area X of the basal ganglia, during the breeding season and during the later stages of sensorimotor song development compared to birds in an earlier stage of sensorimotor development during the fall. These data provide the first evidence that changes in PNN expression could represent a mechanism regulating the closing-reopening of sensitive periods for vocal learning across seasons in adult songbirds.

    更新日期:2019-12-17
  • Two types of memory-based (pantomime) reaches distinguished by gaze anchoring in reach-to-grasp tasks
    Behav. Brain Res. (IF 2.770) Pub Date : 2019-12-16
    Jessica R. Kuntz; Jenni M. Karl; Jon B. Doan; Melody Grohs; Ian Q. Whishaw

    Comparisons of target-based reaching vs memory-based (pantomime) reaching have been used to obtain insight into the visuomotor control of reaching. The present study examined the contribution of gaze anchoring, reaching to a target that is under continuous gaze, to both target-based and memory-based reaching. Participants made target-based reaches for discs located on a table or food items located on a pedestal or they replaced the objects. They then made memory-based reaches in which they pantomimed their target-based reaches. Participants were fitted with hand sensors for kinematic tracking and an eye tracker to monitor gaze. When making target-based reaches, participants directed gaze to the target location from reach onset to offset without interrupting saccades. Similar gaze anchoring was present for memory-based reaches when the surface upon which the target had been placed remained. When the target and its surface were both removed there was no systematic relationship between gaze and the reach. Gaze anchoring was also present when participants replaced a target on a surface, a movement featuring a reach but little grasp. That memory-based reaches can be either gaze anchor-associated or gaze anchor-independent is discussed in relation to contemporary views of the neural control of reaching.

    更新日期:2019-12-17
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