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  • Stress and Seizures: Space, Time and Hippocampal Circuits
    Trends Neurosci. (IF 11.124) Pub Date : 2017-09-12
    B.G. Gunn, T.Z. Baram

    Stress is a major trigger of seizures in people with epilepsy. Exposure to stress results in the release of several stress mediators throughout the brain, including the hippocampus, a region sensitive to stress and prone to seizures. Stress mediators interact with their respective receptors to produce distinct effects on the excitability of hippocampal neurons and networks. Crucially, these stress mediators and their actions exhibit unique spatiotemporal profiles, generating a complex combinatorial output with time- and space-dependent effects on hippocampal network excitability and seizure generation.

  • The Brain Is Needed to Cure Spinal Cord Injury
    Trends Neurosci. (IF 11.124) Pub Date : 2017-09-08
    Tadashi Isa

    Damage to corticospinal fibers in the cervical spinal cord is known to impair dexterous hand movements. However, accumulating evidence has shown that precision grip can recover considerably through rehabilitative training. Recent multidisciplinary studies have revealed that, at the spinal level, this recovery is possible due to an indirect neural pathway through propriospinal neurons (PNs), which relay cortical commands to hand motoneurons. Although this indirect spinal pathway is heavily involved in recovery, its role is dwarfed by a simultaneous large-scale network reorganization spanning motor-related cortices and mesolimbic structures. This large-scale network reorganization is key to the regulation of recovery and future therapeutic strategies will need to take into account the involvement of these supraspinal centers in addition to the known role of the spinal cord.

  • A Self-Killing Rabies Virus That Leaves a Trace on the DNA
    Trends Neurosci. (IF 11.124) Pub Date : 2017-09-07
    William Menegas, Naoshige Uchida, Mitsuko Watabe-Uchida

    Although modified rabies viruses have emerged as a powerful tool for tracing the inputs to genetically defined populations of neurons, the toxicity of the virus has limited its utility. A recent study employed a self-inactivating rabies (SiR) virus that enables recording or manipulation of targeted neurons for months.

  • Cholinergic Control of Information Coding
    Trends Neurosci. (IF 11.124) Pub Date : 2017-07-07
    Jochem van Kempen, Stefano Panzeri, Alexander Thiele

    Specific forms of firing rate correlations can limit efficient information coding in neuronal populations. How this is mitigated is an important topic of current research. A novel study shows that increasing cortical acetylcholine (ACh) levels alter specific aspects of the population correlation structure, which in turn improves population-coding abilities.

  • Acute or Chronic? A Stressful Question
    Trends Neurosci. (IF 11.124) Pub Date : 2017-08-01
    Laura Musazzi, Paolo Tornese, Nathalie Sala, Maurizio Popoli

    Stress is a primary risk factor for neuropsychiatric disorders; at times, even a single trauma can trigger psychopathology. Many rodent models of neuropsychiatric disorders use chronic stress, measuring readouts at the end of long protocols. In a way, traditional chronic models overlook a crucial question: how does the physiological response to stressor(s) turn into a maladaptive pathway that may verge towards psychopathology? Recent evidence suggests that studying the long-term consequences of acute stress would provide critical information on the role of stress in psychopathology. This new conceptual framework could enable us to understand the determinants of a pro-adaptive versus maladaptive trajectory of stress response, and also to study the mechanism of rapid-acting antidepressants, such as ketamine, that target the glutamate system directly.

  • NKCC1 Chloride Importer Antagonists Attenuate Many Neurological and Psychiatric Disorders
    Trends Neurosci. (IF 11.124) Pub Date : 2017-08-14
    Yehezkel Ben-Ari

    In physiological conditions, adult neurons have low intracellular Cl− [(Cl−)I] levels underlying the γ-aminobutyric acid (GABA)ergic inhibitory drive. In contrast, neurons have high (Cl−)I levels and excitatory GABA actions in a wide range of pathological conditions including spinal cord lesions, chronic pain, brain trauma, cerebrovascular infarcts, autism, Rett and Down syndrome, various types of epilepsies, and other genetic or environmental insults. The diuretic highly specific NKCC1 chloride importer antagonist bumetanide (PubChem CID: 2461) efficiently restores low (Cl−)I levels and attenuates many disorders in experimental conditions and in some clinical trials. Here, I review the mechanisms of action, therapeutic effects, promises, and pitfalls of bumetanide.

  • Seizing Control of KCC2: A New Therapeutic Target for Epilepsy
    Trends Neurosci. (IF 11.124) Pub Date : 2017-08-10
    Yvonne E. Moore, Matt R. Kelley, Nicholas J. Brandon, Tarek Z. Deeb, Stephen J. Moss

    Deficits in GABAergic inhibition result in the abnormal neuronal activation and synchronization that underlies seizures. However, the molecular mechanisms responsible for transforming a normal brain into an epileptic one remain largely unknown. Hyperpolarizing inhibition mediated by type A GABA (GABAA) receptors is dependent on chloride extrusion by the neuron-specific type 2 K+–Cl− cotransporter (KCC2). Loss-of-function mutations in KCC2 are a known cause of infantile epilepsy in humans and KCC2 dysfunction is present in patients with both idiopathic and acquired epilepsy. Here we discuss the growing evidence that KCC2 dysfunction has a central role in the development and severity of the epilepsies.

  • All Wrapped Up: Environmental Effects on Myelination
    Trends Neurosci. (IF 11.124) Pub Date : 2017-08-22
    Thomas A. Forbes, Vittorio Gallo

    To date, studies have demonstrated the dynamic influence of exogenous environmental stimuli on multiple regions of the brain. This environmental influence positively and negatively impacts programs governing myelination, and acts on myelinating oligodendrocyte (OL) cells across the human lifespan. Developmentally, environmental manipulation of OL progenitor cells (OPCs) has profound effects on the establishment of functional cognitive, sensory, and motor programs. Furthermore, central nervous system (CNS) myelin remains an adaptive entity in adulthood, sensitive to environmentally induced structural changes. Here, we discuss the role of environmental stimuli on mechanisms governing programs of CNS myelination under normal and pathological conditions. Importantly, we highlight how these extrinsic cues can influence the intrinsic power of myelin plasticity to promote functional recovery.

  • Cellular Computations Underlying Detection of Gaps in Sounds and Lateralizing Sound Sources
    Trends Neurosci. (IF 11.124) Pub Date : 2017-08-31
    Donata Oertel, Xiao-Jie Cao, James R. Ison, Paul D. Allen

    In mammals, acoustic information arises in the cochlea and is transmitted to the ventral cochlear nuclei (VCN). Three groups of VCN neurons extract different features from the firing of auditory nerve fibers and convey that information along separate pathways through the brainstem. Two of these pathways process temporal information: octopus cells detect coincident firing among auditory nerve fibers and transmit signals along monaural pathways, and bushy cells sharpen the encoding of fine structure and feed binaural pathways. The ability of these cells to signal with temporal precision depends on a low-voltage-activated K+ conductance (gKL) and a hyperpolarization-activated conductance (gh). This ‘tale of two conductances’ traces gap detection and sound lateralization to their cellular and biophysical origins.

  • Renewed Attention on the Pupil Light Reflex
    Trends Neurosci. (IF 11.124) Pub Date : 2017-07-07
    Paola Binda, Paul D. Gamlin

    In a recent study, Ebitz and Moore described how subthreshold electrical microstimulation of the macaque frontal eye fields (FEF) modulates the pupillary light reflex. This elegant study suggests that the influence of the FEF and prefrontal cortex on attentional modulation of cortical visual processing extends to the subcortical circuit that mediates a very basic reflex, the pupillary light reflex.

  • Subcortical Contributions to Motor Speech: Phylogenetic, Developmental, Clinical
    Trends Neurosci. (IF 11.124) Pub Date : 2017-07-14
    W. Ziegler, H. Ackermann

    Vocal learning is an exclusively human trait among primates. However, songbirds demonstrate behavioral features resembling human speech learning. Two circuits have a preeminent role in this human behavior; namely, the corticostriatal and the cerebrocerebellar motor loops. While the striatal contribution can be traced back to the avian anterior forebrain pathway (AFP), the sensorimotor adaptation functions of the cerebellum appear to be human specific in acoustic communication. This review contributes to an ongoing discussion on how birdsong translates into human speech. While earlier approaches were focused on higher linguistic functions, we place the motor aspects of speaking at center stage. Genetic data are brought together with clinical and developmental evidence to outline the role of cerebrocerebellar and corticostriatal interactions in human speech.

  • Revolution of Resting-State Functional Neuroimaging Genetics in Alzheimer’s Disease
    Trends Neurosci. (IF 11.124) Pub Date : 2017-07-03
    Patrizia A. Chiesa, Enrica Cavedo, Simone Lista, Paul M. Thompson, Harald Hampel,

    The quest to comprehend genetic, biological, and symptomatic heterogeneity underlying Alzheimer’s disease (AD) requires a deep understanding of mechanisms affecting complex brain systems. Neuroimaging genetics is an emerging field that provides a powerful way to analyze and characterize intermediate biological phenotypes of AD. Here, we describe recent studies showing the differential effect of genetic risk factors for AD on brain functional connectivity in cognitively normal, preclinical, prodromal, and AD dementia individuals. Functional neuroimaging genetics holds particular promise for the characterization of preclinical populations; target populations for disease prevention and modification trials. To this end, we emphasize the need for a paradigm shift towards integrative disease modeling and neuroimaging biomarker-guided precision medicine for AD and other neurodegenerative diseases.

  • The Lateral Habenula and Adaptive Behaviors
    Trends Neurosci. (IF 11.124) Pub Date : 2017-07-05
    Sheri J.Y. Mizumori, Phillip M. Baker

    The evolutionarily conserved lateral habenula (LHb) enables dynamic responses to continually changing contexts and environmental conditions. A model is proposed to account for greater mnemonic and contextual control over LHb-mediated response flexibility as vertebrate brains became more complex. The medial prefrontal cortex (mPFC) provides instructions for context-specific responses to LHb, which assesses the extent to which this response information matches the motivation or internal state of the individual. LHb output either maintains a prior response (match) or leads to alternative responses (mismatch). It may also maintain current spatial and temporal processing in hippocampus (match), or alter such activity to reflect updated trajectory and sequenced information (mismatch). A response flexibility function of the LHb is consistent with poor behavioral control following its disruption (e.g., in depression).

  • Developmental Connectomics from Infancy through Early Childhood
    Trends Neurosci. (IF 11.124) Pub Date : 2017-07-03
    Miao Cao, Hao Huang, Yong He

    The human brain undergoes rapid growth in both structure and function from infancy through early childhood, and this significantly influences cognitive and behavioral development in later life. A newly emerging research framework, developmental connectomics, provides unprecedented opportunities for exploring the developing brain through non-invasive mapping of structural and functional connectivity patterns. Within this framework, we review recent neuroimaging and neurophysiological studies investigating connectome development from 20 postmenstrual weeks to 5 years of age. Specifically, we highlight five fundamental principles of brain network development during the critical first years of life, emphasizing strengthened segregation/integration balance, a remarkable hierarchical order from primary to higher-order regions, unparalleled structural and functional maturations, substantial individual variability, and high vulnerability to risk factors and developmental disorders.

  • Efficient Prevention of Neurodegenerative Diseases by Depletion of Starvation Response Factor Ataxin-2
    Trends Neurosci. (IF 11.124) Pub Date : 2017-07-03
    Georg Auburger, Nesli-Ece Sen, David Meierhofer, Ayşe-Nazlı Başak, Aaron D. Gitler

    Ataxin-2 (ATXN2) homologs exist in all eukaryotic organisms and may have contributed to their origin. Apart from a role in endocytosis, they are known for global effects on mRNA repair and ribosomal translation. Cell size, protein synthesis, and fat and glycogen storage are repressed by ATXN2 via mTORC1 signaling. However, specific liver mitochondrial matrix enzymes and the mitochondrial repair factor PINK1 require ATXN2 abundance. During periods of starvation, ATXN2 is transcriptionally induced and localized to cytosolic stress granules, where nuclear factors dock to compensate RNA pathology. These physiological actions were now revealed to be crucial for human neurodegenerative diseases, given that ATXN2 depletion is surprisingly efficient in preventing motor neuron and cerebellar atrophy, as demonstrated in mouse models, flies, and yeast.

  • Two sources of dopamine for the hippocampus
    Trends Neurosci. (IF 11.124) Pub Date : 2017-05-13
    Colin G. McNamara, David Dupret

    Dopaminergic signalling is established as playing an important role in novelty related modulation of hippocampal memory. Two recent studies have identified the noradrenergic fibres originating in the locus coeruleus as an additional source of neurotransmitter acting on dopaminergic receptors in the hippocampus.

  • Endocannabinoid Signaling in the Control of Social Behavior
    Trends Neurosci. (IF 11.124) Pub Date : 2017-05-26
    Don Wei, Stephen Allsop, Kay Tye, Daniele Piomelli

    Many mammalian species, including humans, exhibit social behavior and form complex social groups. Mechanistic studies in animal models have revealed important roles for the endocannabinoid signaling system, comprising G protein-coupled cannabinoid receptors and their endogenous lipid-derived agonists, in the control of neural processes that underpin social anxiety and social reward, two key aspects of social behavior. An emergent insight from these studies is that endocannabinoid signaling in specific circuits of the brain is context dependent and selectively recruited. These insights open new vistas on the neural basis of social behavior and social impairment.

  • The Role of Interneurons in Autism and Tourette Syndrome
    Trends Neurosci. (IF 11.124) Pub Date : 2017-05-31
    Maximiliano Rapanelli, Luciana Romina Frick, Christopher Pittenger

    The brain includes multiple types of interconnected excitatory and inhibitory neurons that together allow us to move, think, feel, and interact with the environment. Inhibitory interneurons (INs) comprise a small, heterogeneous fraction, but they exert a powerful and tight control over neuronal activity and consequently modulate the magnitude of neuronal output and, ultimately, information processing. IN abnormalities are linked to two pediatric psychiatric disorders with high comorbidity: autism spectrum disorder (ASD) and Tourette syndrome (TS). Studies probing the basis of this link have been contradictory regarding whether the causative mechanism is a reduction in number, dysfunction, or gene aberrant expression (or a combination thereof). Here, we integrate different theories into a more comprehensive view of INs as responsible for the symptomatology observed in these disorders.

  • Adaptive Capacity: An Evolutionary Neuroscience Model Linking Exercise, Cognition, and Brain Health
    Trends Neurosci. (IF 11.124) Pub Date : 2017-06-10
    David A. Raichlen, Gene E. Alexander

    The field of cognitive neuroscience was transformed by the discovery that exercise induces neurogenesis in the adult brain, with the potential to improve brain health and stave off the effects of neurodegenerative disease. However, the basic mechanisms underlying exercise–brain connections are not well understood. We use an evolutionary neuroscience approach to develop the adaptive capacity model (ACM), detailing how and why physical activity improves brain function based on an energy-minimizing strategy. Building on studies showing a combined benefit of exercise and cognitive challenge to enhance neuroplasticity, our ACM addresses two fundamental questions: (i) what are the proximate and ultimate mechanisms underlying age-related brain atrophy, and (ii) how do lifestyle changes influence the trajectory of healthy and pathological aging?

  • Unravelling and Exploiting Astrocyte Dysfunction in Huntington’s Disease
    Trends Neurosci. (IF 11.124) Pub Date : 2017-05-31
    Baljit S. Khakh, Vahri Beaumont, Roger Cachope, Ignacio Munoz-Sanjuan, Steven A. Goldman, Rosemarie Grantyn

    Astrocytes are abundant within mature neural circuits and are involved in brain disorders. Here, we summarize our current understanding of astrocytes and Huntington’s disease (HD), with a focus on correlative and causative dysfunctions of ion homeostasis, calcium signaling, and neurotransmitter clearance, as well as on the use of transplanted astrocytes to produce therapeutic benefit in mouse models of HD. Overall, the data suggest that astrocyte dysfunction is an important contributor to the onset and progression of some HD symptoms in mice. Additional exploration of astrocytes in HD mouse models and humans is needed and may provide new therapeutic opportunities to explore in conjunction with neuronal rescue and repair strategies.

  • Canis familiaris As a Model for Non-Invasive Comparative Neuroscience
    Trends Neurosci. (IF 11.124) Pub Date : 2017-05-29
    Nóra Bunford, Attila Andics, Anna Kis, Ádám Miklósi, Márta Gácsi

    There is an ongoing need to improve animal models for investigating human behavior and its biological underpinnings. The domestic dog (Canis familiaris) is a promising model in cognitive neuroscience. However, before it can contribute to advances in this field in a comparative, reliable, and valid manner, several methodological issues warrant attention. We review recent non-invasive canine neuroscience studies, primarily focusing on (i) variability among dogs and between dogs and humans in cranial characteristics, and (ii) generalizability across dog and dog–human studies. We argue not for methodological uniformity but for functional comparability between methods, experimental designs, and neural responses. We conclude that the dog may become an innovative and unique model in comparative neuroscience, complementing more traditional models.

  • Seq-ing the Circuit Logic of the Basal Ganglia
    Trends Neurosci. (IF 11.124) Pub Date : 2017-05-10
    Ricardo Hernandez-Martinez, Nicole Calakos

    Recently, Wallace et al. (2017) provide an unprecedented view of the layers of molecular, cellular and circuit complexity involving a basal ganglia output structure, the entopeduncular nucleus. Their findings lend order to chaos by revealing how molecularly and functionally defined cellular subsets are organized into distinct circuitry.

  • Sustained Activity Encoding Working Memories: Not Fully Distributed
    Trends Neurosci. (IF 11.124) Pub Date : 2017-05-14
    Matthew L. Leavitt, Diego Mendoza-Halliday, Julio C. Martinez-Trujillo

    Working memory (WM) is the ability to remember and manipulate information for short time intervals. Recent studies have proposed that sustained firing encoding the contents of WM is ubiquitous across cortical neurons. We review here the collective evidence supporting this claim. A variety of studies report that neurons in prefrontal, parietal, and inferotemporal association cortices show robust sustained activity encoding the location and features of memoranda during WM tasks. However, reports of WM-related sustained activity in early sensory areas are rare, and typically lack stimulus specificity. We propose that robust sustained activity that can support WM coding arises as a property of association cortices downstream from the early stages of sensory processing.

  • Synaptic Impairment in Alzheimer’s Disease: A Dysregulated Symphony
    Trends Neurosci. (IF 11.124) Pub Date : 2017-05-08
    Stefania Forner, David Baglietto-Vargas, Alessandra C. Martini, Laura Trujillo-Estrada, Frank M. LaFerla

    Alzheimer’s disease (AD) is characterized by memory loss, cognitive decline, and devastating neurodegeneration, not only as a result of the extracellular accumulation of beta-amyloid peptide (Aβ) and intracellular accumulation of tau, but also as a consequence of the dysfunction and loss of synapses. Although significant advances have been made in our understanding of the relationship of the pathological role of Aβ and tau in synapse dysfunction, several questions remain as to how Aβ and tau interdependently cause impairments in synaptic function in AD. Overall, more insight into these questions should enable researchers in this field to develop novel therapeutic targets to mitigate or delay the cognitive deficits associated with this devastating disease.

  • The Role of Astrocyte Dysfunction in Parkinson’s Disease Pathogenesis
    Trends Neurosci. (IF 11.124) Pub Date : 2017-05-17
    Heather D.E. Booth, Warren D. Hirst, Richard Wade-Martins

    Astrocytes are the most populous glial subtype and are critical for brain function. Despite this, historically there have been few studies into the role that they may have in neurodegenerative diseases, such as Parkinson’s disease (PD). Recently, however, several studies have determined that genes known to have a causative role in the development of PD are expressed in astrocytes and have important roles in astrocyte function. Here, we review these recent developments and discuss their impact on our understanding of the pathophysiology of PD, and the implications that this might have for its treatment.

  • Aberrant Network Activity in Schizophrenia
    Trends Neurosci. (IF 11.124) Pub Date : 2017-05-14
    Mark J. Hunt, Nancy J. Kopell, Roger D. Traub, Miles A. Whittington

    Brain dynamic changes associated with schizophrenia are largely equivocal, with interpretation complicated by many factors, such as the presence of therapeutic agents and the complex nature of the syndrome itself. Evidence for a brain-wide change in individual network oscillations, shared by all patients, is largely equivocal, but stronger for lower (delta) than for higher (gamma) bands. However, region-specific changes in rhythms across multiple, interdependent, nested frequencies may correlate better with pathology. Changes in synaptic excitation and inhibition in schizophrenia disrupt delta rhythm-mediated cortico-cortical communication, while enhancing thalamocortical communication in this frequency band. The contrasting relationships between delta and higher frequencies in thalamus and cortex generate frequency mismatches in inter-regional connectivity, leading to a disruption in temporal communication between higher-order brain regions associated with mental time travel.

  • The Significance of Memory in Sensory Cortex
    Trends Neurosci. (IF 11.124) Pub Date : 2017-03-28
    Lars Muckli, Lucy S. Petro

    Early sensory cortex is typically investigated in response to sensory stimulation, masking the contribution of internal signals. Recently, van Kerkoerle and colleagues reported that attention and memory signals segregate from sensory signals within specific layers of primary visual cortex, providing insight into the role of internal signals in sensory processing.

  • The Role of Mental Maps in Decision-Making
    Trends Neurosci. (IF 11.124) Pub Date : 2017-03-30
    Raphael Kaplan, Nicolas W. Schuck, Christian F. Doeller

    A growing body of work is investigating the use of mental maps during decision-making. Here we discuss how decision-making organizes experiences according to an internal model of the current task, thereby structuring memory. Likewise, we consider how the structure of mental maps contributes to decision-making.

  • Deciphering Neural Codes of Memory during Sleep
    Trends Neurosci. (IF 11.124) Pub Date : 2017-04-05
    Zhe Chen, Matthew A. Wilson

    Memories of experiences are stored in the cerebral cortex. Sleep is critical for the consolidation of hippocampal memory of wake experiences into the neocortex. Understanding representations of neural codes of hippocampal–neocortical networks during sleep would reveal important circuit mechanisms in memory consolidation and provide novel insights into memory and dreams. Although sleep-associated ensemble spike activity has been investigated, identifying the content of memory in sleep remains challenging. Here we revisit important experimental findings on sleep-associated memory (i.e., neural activity patterns in sleep that reflect memory processing) and review computational approaches to the analysis of sleep-associated neural codes (SANCs). We focus on two analysis paradigms for sleep-associated memory and propose a new unsupervised learning framework (‘memory first, meaning later’) for unbiased assessment of SANCs.

  • Chloride Dysregulation, Seizures, and Cerebral Edema: A Relationship with Therapeutic Potential
    Trends Neurosci. (IF 11.124) Pub Date : 2017-04-18
    Joseph Glykys, Volodymyr Dzhala, Kiyoshi Egawa, Kristopher T. Kahle, Eric Delpire, Kevin Staley

    Pharmacoresistant seizures and cytotoxic cerebral edema are serious complications of ischemic and traumatic brain injury. Intraneuronal Cl− concentration ([Cl−]i) regulation impacts on both cell volume homeostasis and Cl−-permeable GABAA receptor-dependent membrane excitability. Understanding the pleiotropic molecular determinants of neuronal [Cl−]i − cytoplasmic impermeant anions, polyanionic extracellular matrix (ECM) glycoproteins, and plasmalemmal Cl− transporters − could help the identification of novel anticonvulsive and neuroprotective targets. The cation/Cl− cotransporters and ECM metalloproteinases may be particularly druggable targets for intervention. We establish here a paradigm that accounts for recent data regarding the complex regulatory mechanisms of neuronal [Cl−]i and how these mechanisms impact on neuronal volume and excitability. We propose approaches to modulate [Cl−]i that are relevant for two common clinical sequela of brain injury: edema and seizures.

  • Neural Cell Adhesion Molecules of the Immunoglobulin Superfamily Regulate Synapse Formation, Maintenance, and Function
    Trends Neurosci. (IF 11.124) Pub Date : 2017-03-27
    Vladimir Sytnyk, Iryna Leshchyns’ka, Melitta Schachner

    Immunoglobulin superfamily adhesion molecules are among the most abundant proteins in vertebrate and invertebrate nervous systems. Prominent family members are the neural cell adhesion molecules NCAM and L1, which were the first to be shown to be essential not only in development but also in synaptic function and as key regulators of synapse formation, synaptic activity, plasticity, and synaptic vesicle recycling at distinct developmental and activity stages. In addition to interacting with each other, adhesion molecules interact with ion channels and cytokine and neurotransmitter receptors. Mutations in their genes are linked to neurological disorders associated with abnormal development and synaptic functioning. This review presents an overview of recent studies on these molecules and their crucial impact on neurological disorders.

  • The Sleeping Cerebellum
    Trends Neurosci. (IF 11.124) Pub Date : 2017-04-18
    Cathrin B. Canto, Yoshiyuki Onuki, Bastiaan Bruinsma, Ysbrand D. van der Werf, Chris I. De Zeeuw

    We sleep almost one-third of our lives and sleep plays an important role in critical brain functions like memory formation and consolidation. The role of sleep in cerebellar processing, however, constitutes an enigma in the field of neuroscience; we know little about cerebellar sleep-physiology, cerebro–cerebellar interactions during sleep, or the contributions of sleep to cerebellum-dependent memory consolidation. Likewise, we do not understand why cerebellar malfunction can lead to changes in the sleep–wake cycle and sleep disorders. In this review, we evaluate how sleep and cerebellar processing may influence one another and highlight which scientific routes and technical approaches could be taken to uncover the mechanisms underlying these interactions.

  • Monoamine Transporters as Ionotropic Receptors
    Trends Neurosci. (IF 11.124) Pub Date : 2017-03-18
    Louis J. De Felice

    It is well established that glutamate and GABA signal through both ionotropic and metabotropic receptors. Conversely, it is thought that, with one exception, monoamines (dopamine, serotonin, and norepinephrine) signal via metabotropic receptors. Given their capacity to generate fast-acting currents, I suggest that the monoamine transporters should be considered as ionotropic receptors.

  • The Neuroethological Paradox of Animal Consciousness
    Trends Neurosci. (IF 11.124) Pub Date : 2017-03-06
    Yoram Gutfreund

    The more advanced our understanding of the brain of an animal is, the less likely that this animal is a conscious being. This provocative logical paradox is explained and analyzed, leading to the conclusion that to advance understanding of animal consciousness it is necessary to resolve first how our consciousness is produced by our brain.

  • The Insula: An Underestimated Brain Area in Clinical Neuroscience, Psychiatry, and Neurology
    Trends Neurosci. (IF 11.124) Pub Date : 2017-03-15
    Ho Namkung, Sun-Hong Kim, Akira Sawa

    Supported by recent human neuroimaging studies, the insula is re-emerging as an important brain area not only in the physiological understanding of the brain, but also in pathological contexts in clinical research. In this opinion article, we briefly introduce the anatomical and histological features of the human insula. We then summarize the physiological functions of the insula and underscore its pathological roles in psychiatric and neurological disorders that have long been underestimated. We finally propose possible strategies through which the role of the insula may be further understood for both basic and clinical neuroscience.

  • Where Does EEG Come From and What Does It Mean?
    Trends Neurosci. (IF 11.124) Pub Date : 2017-03-15
    Michael X Cohen

    Electroencephalography (EEG) has been instrumental in making discoveries about cognition, brain function, and dysfunction. However, where do EEG signals come from and what do they mean? The purpose of this paper is to argue that we know shockingly little about the answer to this question, to highlight what we do know, how important the answers are, and how modern neuroscience technologies that allow us to measure and manipulate neural circuits with high spatiotemporal accuracy might finally bring us some answers. Neural oscillations are perhaps the best feature of EEG to use as anchors because oscillations are observed and are studied at multiple spatiotemporal scales of the brain, in multiple species, and are widely implicated in cognition and in neural computations.

  • Physiological Markers of Motor Inhibition during Human Behavior
    Trends Neurosci. (IF 11.124) Pub Date : 2017-03-21
    Julie Duque, Ian Greenhouse, Ludovica Labruna, Richard B. Ivry

    Transcranial magnetic stimulation (TMS) studies in humans have shown that many behaviors engage processes that suppress excitability within the corticospinal tract. Inhibition of the motor output pathway has been extensively studied in the context of action stopping, where a planned movement needs to be abruptly aborted. Recent TMS work has also revealed markers of motor inhibition during the preparation of movement. Here, we review the evidence for motor inhibition during action stopping and action preparation, focusing on studies that have used TMS to monitor changes in the excitability of the corticospinal pathway. We discuss how these physiological results have motivated theoretical models of how the brain selects actions, regulates movement initiation and execution, and switches from one state to another.

  • Obesity-Induced Neuroinflammation: Beyond the Hypothalamus
    Trends Neurosci. (IF 11.124) Pub Date : 2017-03-18
    Owein Guillemot-Legris, Giulio G. Muccioli

    Obesity is now a worldwide health issue. Far from being limited to weight gain, obesity is generally associated with low-grade inflammation and with a cluster of disorders collectively known as the ‘metabolic syndrome’. When considering obesity and the subsequent neuroinflammation, the focus was long set on the hypothalamus. More recently, obesity-derived neuroinflammation has been shown to affect other brain structures such as the hippocampus, cortex, brainstem, or amygdala. Furthermore, obesity has been associated with increased occurrence of central disorders such as depression and impaired cognitive function. We discuss here the effects and mechanisms of obesity-derived neuroinflammation, with a specific emphasis on extra-hypothalamic structures, as well as the repercussions of neuroinflammation for some cerebral functions.

  • Shaping Science for Increasing Interdependence and Specialization
    Trends Neurosci. (IF 11.124) Pub Date : 2017-01-23
    Christian Utzerath, Guillén Fernández

    Like art, science affords an individualistic career. However, increasingly, complexity necessitates increased interdependency and specialization. Despite this change, many institutions, funding agencies, and publishers insist on an exclusively individualistic model of science. This hinders scientific progress by imposing a range of inefficiencies in the planning and execution of research plans.

  • Cannabidiol: Swinging the Marijuana Pendulum From ‘Weed’ to Medication to Treat the Opioid Epidemic
    Trends Neurosci. (IF 11.124) Pub Date : 2017-02-02
    Yasmin L. Hurd

    Epidemics require a paradigm shift in thinking about all possible solutions. The rapidly changing sociopolitical marijuana landscape provides a foundation for the therapeutic development of medicinal cannabidiol to address the current opioid abuse crisis.

  • Neuronal Adaptation: Tired Neurons or Wired Networks?
    Trends Neurosci. (IF 11.124) Pub Date : 2016-12-22
    J. Patrick Mayo, Matthew A. Smith

    Neuronal adaptation – time-dependent modulation of sensory responses following sequential stimuli – is thought to be a consequence of synaptic plasticity. But recent, empirically-grounded, modeling by Quiroga and colleagues demonstrates that the adaptation of visual cortical responses can be described by recurrent network connections with fixed synaptic weights.

  • Advancing NMDA Receptor Physiology by Integrating Multiple Approaches
    Trends Neurosci. (IF 11.124) Pub Date : 2017-02-08
    Huan-Xiang Zhou, Lonnie P. Wollmuth

    NMDA receptors (NMDARs) are ion channels activated by the excitatory neurotransmitter glutamate and are essential to all aspects of brain function, including learning and memory formation. Missense mutations distributed throughout NMDAR subunits have been associated with an array of neurological disorders. Recent structural, functional, and computational studies have generated many insights into the activation process connecting glutamate binding to ion-channel opening, which is central to NMDAR physiology and pathophysiology. The field appears poised for breakthroughs, including the exciting prospect of resolving the conformations and energetics of elementary steps in the activation process, and atomic-level modeling of the effects of missense mutations on receptor function. The most promising strategy going forward is through strong integration of multiple approaches.

Some contents have been Reproduced with permission of the American Chemical Society.
Some contents have been Reproduced by permission of The Royal Society of Chemistry.