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  • Astrocytes: Heterogeneous and Dynamic Phenotypes in Neurodegeneration and Innate Immunity
    Neuroscientist (IF 7.461) Pub Date : 2018-11-17
    Colm Cunningham; Aisling Dunne; Ana Belen Lopez-Rodriguez

    Astrocytes are the most numerous cell type in the brain and perform several essential functions in supporting neuronal metabolism and actively participating in neural circuit and behavioral function. They also have essential roles as innate immune cells in responding to local neuropathology, and the manner in which they respond to brain injury and degeneration is the subject of increasing attention in neuroscience. Although activated astrocytes have long been thought of as a relatively homogenous population, which alter their phenotype in a relatively stereotyped way upon central nervous system injury, the last decade has revealed substantial heterogeneity in the basal state and significant heterogeneity of phenotype during reactive astrocytosis. Thus, phenotypic diversity occurs at two distinct levels: that determined by regionality and development and that determined by temporally dynamic changes to the environment of astrocytes during pathology. These inflammatory and pathological states shape the phenotype of these cells, with different consequences for destruction or recovery of the local tissue, and thus elucidating these phenotypic changes has significant therapeutic implications. In this review, we will focus on the phenotypic heterogeneity of astrocytes in health and disease and their propensity to change that phenotype upon subsequent stimuli.

    更新日期:2018-11-17
  • Are We “Motorically” Wired to Others? High-Level Motor Computations and Their Role in Autism
    Neuroscientist (IF 7.461) Pub Date : 2017-12-22
    Luca Casartelli; Alessandra Federici; Emilia Biffi; Massimo Molteni; Luca Ronconi

    High-level motor computations reflect abstract components far apart from the mere motor performance. Neural correlates of these computations have been explored both in nonhuman and human primates, supporting the idea that our brain recruits complex nodes for motor representations. Of note, these computations have exciting implications for social cognition, and they also entail important challenges in the context of autism. Here, we focus on these challenges benefiting from recent studies addressing motor interference, motor resonance, and high-level motor planning. In addition, we suggest new ideas about how one maps and shares the (motor) space with others. Taken together, these issues inspire intriguing and fascinating questions about the social tendency of our high-level motor computations, and this tendency may indicate that we are “motorically” wired to others. Thus, after furnishing preliminary insights on putative neural nodes involved in these computations, we focus on how the hypothesized social nature of high-level motor computations may be anomalous or limited in autism, and why this represents a critical challenge for the future.

    更新日期:2018-11-08
  • Orientation Encoding and Viewpoint Invariance in Face Recognition: Inferring Neural Properties from Large-Scale Signals
    Neuroscientist (IF 7.461) Pub Date : 2018-06-01
    Fernando M. Ramírez

    Viewpoint-invariant face recognition is thought to be subserved by a distributed network of occipitotemporal face-selective areas that, except for the human anterior temporal lobe, have been shown to also contain face-orientation information. This review begins by highlighting the importance of bilateral symmetry for viewpoint-invariant recognition and face-orientation perception. Then, monkey electrophysiological evidence is surveyed describing key tuning properties of face-selective neurons—including neurons bimodally tuned to mirror-symmetric face-views—followed by studies combining functional magnetic resonance imaging (fMRI) and multivariate pattern analyses to probe the representation of face-orientation and identity information in humans. Altogether, neuroimaging studies suggest that face-identity is gradually disentangled from face-orientation information along the ventral visual processing stream. The evidence seems to diverge, however, regarding the prevalent form of tuning of neural populations in human face-selective areas. In this context, caveats possibly leading to erroneous inferences regarding mirror-symmetric coding are exposed, including the need to distinguish angular from Euclidean distances when interpreting multivariate pattern analyses. On this basis, this review argues that evidence from the fusiform face area is best explained by a view-sensitive code reflecting head angular disparity, consistent with a role of this area in face-orientation perception. Finally, the importance is stressed of explicit models relating neural properties to large-scale signals.

    更新日期:2018-11-08
  • Neural Oscillations Orchestrate Multisensory Processing
    Neuroscientist (IF 7.461) Pub Date : 2018-02-09
    Julian Keil; Daniel Senkowski

    At any given moment, we receive input through our different sensory systems, and this information needs to be processed and integrated. Multisensory processing requires the coordinated activity of distinct cortical areas. Key mechanisms implicated in these processes include local neural oscillations and functional connectivity between distant cortical areas. Evidence is now emerging that neural oscillations in distinct frequency bands reflect different mechanisms of multisensory processing. Moreover, studies suggest that aberrant neural oscillations contribute to multisensory processing deficits in clinical populations, such as schizophrenia. In this article, we review recent literature on the neural mechanisms underlying multisensory processing, focusing on neural oscillations. We derive a framework that summarizes findings on (1) stimulus-driven multisensory processing, (2) the influence of top-down information on multisensory processing, and (3) the role of predictions for the formation of multisensory perception. We propose that different frequency band oscillations subserve complementary mechanisms of multisensory processing. These processes can act in parallel and are essential for multisensory processing.

    更新日期:2018-11-08
  • Epigenetic Control of Schwann Cells
    Neuroscientist (IF 7.461) Pub Date : 2018-01-07
    Ki H. Ma; John Svaren

    The journey of Schwann cells from their origin in the neural crest to their ensheathment and myelination of peripheral nerves is a remarkable one. Their apparent static function in enabling saltatory conduction of mature nerve is not only vital for long-term health of peripheral nerve but also belies an innate capacity of terminally differentiated Schwann cells to radically alter their differentiation status in the face of nerve injury. The transition from migrating neural crest cells to nerve ensheathment, and then myelination of large diameter axons has been characterized extensively and several of the transcriptional networks have been identified. However, transcription factors must also modify chromatin structure during Schwann cell maturation and this review will focus on chromatin modification machinery that is involved in promoting the transition to, and maintenance of, myelinating Schwann cells. In addition, Schwann cells are known to play important regenerative roles after peripheral nerve injury, and information on epigenomic reprogramming of the Schwann cell genome has emerged. Characterization of epigenomic requirements for myelin maintenance and Schwann cell responses to injury will be vital in understanding how the various Schwann cell functions can be optimized to maintain and repair peripheral nerve function.

    更新日期:2018-11-08
  • The Ubiquitin-Proteasome System and Memory: Moving Beyond Protein Degradation
    Neuroscientist (IF 7.461) Pub Date : 2018-03-12
    Timothy J. Jarome; Rishi K. Devulapalli

    Cellular models of memory formation have focused on the need for protein synthesis. Recently, evidence has emerged that protein degradation mediated by the ubiquitin-proteasome system (UPS) is also important for this process. This has led to revised cellular models of memory formation that focus on a balance between protein degradation and synthesis. However, protein degradation is only one function of the UPS. Studies using single-celled organisms have shown that non-proteolytic ubiquitin-proteasome signaling is involved in histone modifications and DNA methylation, suggesting that ubiquitin and the proteasome can regulate chromatin remodeling independent of protein degradation. Despite this evidence, the idea that the UPS is more than a protein degradation pathway has not been examined in the context of memory formation. In this article, we summarize recent findings implicating protein degradation in memory formation and discuss various ways in which both ubiquitin signaling and the proteasome could act independently to regulate epigenetic-mediated transcriptional processes necessary for learning-dependent synaptic plasticity. We conclude by proposing comprehensive models of how non-proteolytic functions of the UPS could work in concert to control epigenetic regulation of the cellular memory consolidation process, which will serve as a framework for future studies examining the role of the UPS in memory formation.

    更新日期:2018-11-08
  • Neuroimaging of the Injured Pediatric Brain: Methods and New Lessons
    Neuroscientist (IF 7.461) Pub Date : 2018-02-28
    Emily L. Dennis; Talin Babikian; Christopher C. Giza; Paul M. Thompson; Robert F. Asarnow

    Traumatic brain injury (TBI) is a significant public health problem in the United States, especially for children and adolescents. Current epidemiological data estimate over 600,000 patients younger than 20 years are treated for TBI in emergency rooms annually. While many patients experience a full recovery, for others there can be long-lasting cognitive, neurological, psychological, and behavioral disruptions. TBI in youth can disrupt ongoing brain development and create added family stress during a formative period. The neuroimaging methods used to assess brain injury improve each year, providing researchers a more detailed characterization of the injury and recovery process. In this review, we cover current imaging methods used to quantify brain disruption post-injury, including structural magnetic resonance imaging (MRI), diffusion MRI, functional MRI, resting state fMRI, and magnetic resonance spectroscopy (MRS), with brief coverage of other methods, including electroencephalography (EEG), single-photon emission computed tomography (SPECT), and positron emission tomography (PET). We include studies focusing on pediatric moderate-severe TBI from 2 months post-injury and beyond. While the morbidity of pediatric TBI is considerable, continuing advances in imaging methods have the potential to identify new treatment targets that can lead to significant improvements in outcome.

    更新日期:2018-11-08
  • Low Back Pain: The Potential Contribution of Supraspinal Motor Control and Proprioception
    Neuroscientist (IF 7.461) Pub Date : 2018-11-02
    Michael Lukas Meier; Andrea Vrana; Petra Schweinhardt

    Motor control, which relies on constant communication between motor and sensory systems, is crucial for spine posture, stability and movement. Adaptions of motor control occur in low back pain (LBP) while different motor adaption strategies exist across individuals, probably to reduce LBP and risk of injury. However, in some individuals with LBP, adapted motor control strategies might have long-term consequences, such as increased spinal loading that has been linked with degeneration of intervertebral discs and other tissues, potentially maintaining recurrent or chronic LBP. Factors contributing to motor control adaptations in LBP have been extensively studied on the motor output side, but less attention has been paid to changes in sensory input, specifically proprioception. Furthermore, motor cortex reorganization has been linked with chronic and recurrent LBP, but underlying factors are poorly understood. Here, we review current research on behavioral and neural effects of motor control adaptions in LBP. We conclude that back pain-induced disrupted or reduced proprioceptive signaling likely plays a pivotal role in driving long-term changes in the top-down control of the motor system via motor and sensory cortical reorganization. In the outlook of this review, we explore whether motor control adaptations are also important for other (musculoskeletal) pain conditions.

    更新日期:2018-11-05
  • Brain-Derived Neurotrophic Factor (BDNF): Novel Insights into Regulation and Genetic Variation
    Neuroscientist (IF 7.461) Pub Date : 2018-11-02
    Michael Notaras; Maarten van den Buuse

    Since its discovery, brain-derived neurotrophic factor (BDNF) has spawned a literature that now spans 35 years of research. While all neurotrophins share considerable overlap in sequence homology and their processing, BDNF has become the most widely studied neurotrophin because of its broad roles in brain homeostasis, health, and disease. Although research on BDNF has produced thousands of articles, there remain numerous long-standing questions on aspects of BDNF molecular biology and signaling. Here we provide a comprehensive review, including both a historical narrative and a forward-looking perspective on advances in the actions of BDNF within the brain. We specifically review BDNF’s gene structure, peptide composition (including domains, posttranslational modifications and putative motif sites), mechanisms of transport, signaling pathway recruitment, and other recent developments including the functional effects of genetic variation and the discovery of a new BDNF prodomain ligand. This body of knowledge illustrates a highly conserved and complex role for BDNF within the brain, that promotes the idea that the neurotrophin biology of BDNF is diverse and that any disease involvement is likely to be equally multifarious.

    更新日期:2018-11-05
  • Thinking Outside the Box (and Arrow): Current Themes in Striatal Dysfunction in Movement Disorders
    Neuroscientist (IF 7.461) Pub Date : 2018-10-31
    Joshua L. Plotkin; Joshua A. Goldberg

    The basal ganglia are an intricately connected assembly of subcortical nuclei, forming the core of an adaptive network connecting cortical and thalamic circuits. For nearly three decades, researchers and medical practitioners have conceptualized how the basal ganglia circuit works, and how its pathology underlies motor disorders such as Parkinson’s and Huntington’s diseases, using what is often referred to as the “box-and-arrow model”: a circuit diagram showing the broad strokes of basal ganglia connectivity and the pathological increases and decreases in the weights of specific connections that occur in disease. While this model still has great utility and has led to groundbreaking strategies to treat motor disorders, our evolving knowledge of basal ganglia function has made it clear that this classic model has several shortcomings that severely limit its predictive and descriptive abilities. In this review, we will focus on the striatum, the main input nucleus of the basal ganglia. We describe recent advances in our understanding of the rich microcircuitry and plastic capabilities of the striatum, factors not captured by the original box-and-arrow model, and provide examples of how such advances inform our current understanding of the circuit pathologies underlying motor disorders.

    更新日期:2018-11-02
  • GABAergic Interneurons in Seizures: Investigating Causality With Optogenetics
    Neuroscientist (IF 7.461) Pub Date : 2018-10-15
    Vincent Magloire; Marion S. Mercier; Dimitri M. Kullmann; Ivan Pavlov

    Seizures are complex pathological network events characterized by excessive and hypersynchronized activity of neurons, including a highly diverse population of GABAergic interneurons. Although the primary function of inhibitory interneurons under normal conditions is to restrain excitation in the brain, this system appears to fail intermittently, allowing runaway excitation. Recent developments in optogenetics, combined with genetic tools and advanced electrophysiological and imaging techniques, allow us for the first time to assess the causal roles of identified cell-types in network dynamics. While these methods have greatly increased our understanding of cortical microcircuits in epilepsy, the roles played by individual GABAergic cell-types in controlling ictogenesis remain incompletely resolved. Indeed, the ability of interneurons to suppress epileptic discharges varies across different subtypes, and an accumulating body of evidence paradoxically implicates some interneuron subtypes in the initiation and maintenance of epileptiform activity. Here, we bring together findings from this growing field and discuss what can be inferred regarding the causal role of different GABAergic cell-types in seizures.

    更新日期:2018-10-15
  • Twitches, Blinks, and Fidgets: Important Generators of Ongoing Neural Activity
    Neuroscientist (IF 7.461) Pub Date : 2018-10-12
    Patrick J. Drew; Aaron T. Winder; Qingguang Zhang

    Animals and humans continuously engage in small, spontaneous motor actions, such as blinking, whisking, and postural adjustments (“fidgeting”). These movements are accompanied by changes in neural activity in sensory and motor regions of the brain. The frequency of these motions varies in time, is affected by sensory stimuli, arousal levels, and pathology. These fidgeting behaviors can be entrained by sensory stimuli. Fidgeting behaviors will cause distributed, bilateral functional activation in the 0.01 to 0.1 Hz frequency range that will show up in functional magnetic resonance imaging and wide-field calcium neuroimaging studies, and will contribute to the observed functional connectivity among brain regions. However, despite the large potential of these behaviors to drive brain-wide activity, these fidget-like behaviors are rarely monitored. We argue that studies of spontaneous and evoked brain dynamics in awake animals and humans should closely monitor these fidgeting behaviors. Differences in these fidgeting behaviors due to arousal or pathology will “contaminate” ongoing neural activity, and lead to apparent differences in functional connectivity. Monitoring and accounting for the brain-wide activations by these behaviors is essential during experiments to differentiate fidget-driven activity from internally driven neural dynamics.

    更新日期:2018-10-12
  • Region-Specific Phenotypes of Microglia: The Role of Local Regulatory Cues
    Neuroscientist (IF 7.461) Pub Date : 2018-10-03
    Lindsay M. De Biase; Antonello Bonci

    Microglia are ubiquitous, macrophage like cells within the central nervous system (CNS) that play critical roles in supporting neuronal health and viability. They can also influence neuronal membrane properties and synaptic connectivity, positioning microglia as key cellular players in both physiological and pathological contexts. Microglia have generally been assumed to be equivalent throughout the CNS, but accumulating evidence indicates that their properties vary substantially across distinct CNS regions. In comparison to our understanding of neuronal diversity and its functional importance, our knowledge about causes and consequences of microglial regional heterogeneity is extremely limited. To fully understand how microglia influence the function of specific neuronal populations and shape heightened susceptibility of some neurons to damage and disease, greater focus on microglial heterogeneity is needed.

    更新日期:2018-10-03
  • Functional and Neuroanatomical Bases of Developmental Stuttering: Current Insights
    Neuroscientist (IF 7.461) Pub Date : 2018-09-28
    Soo-Eun Chang; Emily O. Garnett; Andrew Etchell; Ho Ming Chow

    Affecting 5% of all preschool-aged children and 1% of the general population, developmental stuttering—also called childhood-onset fluency disorder—is a complex, multifactorial neurodevelopmental disorder characterized by frequent disruption of the fluent flow of speech. Over the past two decades, neuroimaging studies of both children and adults who stutter have begun to provide significant insights into the neurobiological bases of stuttering. This review highlights convergent findings from this body of literature with a focus on functional and structural neuroimaging results that are supported by theoretically driven neurocomputational models of speech production. Updated views on possible mechanisms of stuttering onset and persistence, and perspectives on promising areas for future research into the mechanisms of stuttering, are discussed.

    更新日期:2018-09-28
  • A Brain on a Roller Coaster: Can the Dopamine Reward System Act as a Protagonist to Subdue the Ups and Downs of Bipolar Disorder?
    Neuroscientist (IF 7.461) Pub Date : 2017-06-14
    Shokouh Arjmand; Mina Behzadi; Gary J. Stephens; Sara Ezzatabadipour; Rostam Seifaddini; Shahrad Arjmand; Mohammad Shabani

    One of the most interesting but tenebrous parts of the bipolar disorder (BD) story is the switch between (hypo)mania and depression, which can give bipolar patients a thrilling, but somewhat perilous, ‘ride’. Numerous studies have pointed out that there are some recognizable differences (either state-dependent or state-independent) in several brain regions of people with BD, including components of the brain’s reward system. Understanding the underpinning mechanisms of high and low mood statuses in BD has potential, not only for the development of highly specific and selective pharmaceutical agents, but also for better treatment approaches and psychological interventions to manage BD and, thus, give patients a safer ride. Herein, we review evidence that supports involvement of the reward system in the pathophysiology of mood swings, with the main focus on the mesocorticolimbic dopaminergic neural circuitry. Principally using findings from neuroimaging studies, we aim to signpost readers as to how mood alterations may affect different areas of the reward system and how antipsychotic drugs can influence the activity of these brain areas. Finally, we critically evaluate the hypothesis that the mesocorticolimbic dopamine reward system may act as a functional rheostat for different mood states.

    更新日期:2018-08-30
  • Pericytes Make Spinal Cord Breathless after Injury
    Neuroscientist (IF 7.461) Pub Date : 2017-09-21
    Viviani M. Almeida; Ana E. Paiva; Isadora F. G. Sena; Akiva Mintz; Luiz Alexandre V. Magno; Alexander Birbrair

    Traumatic spinal cord injury is a devastating condition that leads to significant neurological deficits and reduced quality of life. Therapeutic interventions after spinal cord lesions are designed to address multiple aspects of the secondary damage. However, the lack of detailed knowledge about the cellular and molecular changes that occur after spinal cord injury restricts the design of effective treatments. Li and colleagues using a rat model of spinal cord injury and in vivo microscopy reveal that pericytes play a key role in the regulation of capillary tone and blood flow in the spinal cord below the site of the lesion. Strikingly, inhibition of specific proteins expressed by pericytes after spinal cord injury diminished hypoxia and improved motor function and locomotion of the injured rats. This work highlights a novel central cellular population that might be pharmacologically targeted in patients with spinal cord trauma. The emerging knowledge from this research may provide new approaches for the treatment of spinal cord injury.

    更新日期:2018-08-30
  • You Can Observe a Lot by Watching: Hughlings Jackson’s Underappreciated and Prescient Ideas about Brain Control of Movement
    Neuroscientist (IF 7.461) Pub Date : 2018-06-14
    Ari Berkowitz

    John Hughlings Jackson, the 19th-century British neurologist, first described what are today called Jacksonian seizures. He is generally associated with somatotopy, the idea that neighboring brain regions control neighboring body parts, as later represented pictorially in Wilder Penfield’s “homunculus,” or little man in the brain. Jackson’s own views, however, were quite different, though this is seldom appreciated. In an 1870 article, Jackson advanced the hypotheses that each region of the cerebrum controls movements of multiple body parts, but to different degrees, and that the “march” of movements that typically occurs during Jacksonian seizures is caused by the downstream connections of the overactive neurons at the seizure focus, rather than a somatotopic organization of the cerebrum. Jackson’s hypotheses, which were based almost entirely on his careful observations of movements during seizures, are well within the range of current hypotheses about how the frontal lobe is organized to control movements and thus deserve renewed attention.

    更新日期:2018-08-30
  • Versatility and Flexibility of Cortical Circuits
    Neuroscientist (IF 7.461) Pub Date : 2017-09-21
    Melissa S. Haley; Arianna Maffei

    Cortical circuits are known to be plastic and adaptable, as shown by an impressive body of evidence demonstrating the ability of cortical circuits to adapt to changes in environmental stimuli, development, learning, and insults. In this review, we will discuss some of the features of cortical circuits that are thought to facilitate cortical circuit versatility and flexibility. Throughout life, cortical circuits can be extensively shaped and refined by experience while preserving their overall organization, suggesting that mechanisms are in place to favor change but also to stabilize some aspects of the circuit. First, we will describe the basic organization and some of the common features of cortical circuits. We will then discuss how this underlying cortical structure provides a substrate for the experience- and learning-dependent processes that contribute to cortical flexibility.

    更新日期:2018-08-30
  • Epigenome Interactions with Patterned Neuronal Activity
    Neuroscientist (IF 7.461) Pub Date : 2018-02-27
    Jillian Belgrad; R. Douglas Fields

    The temporal coding of action potential activity is fundamental to nervous system function. Here we consider how gene expression in neurons is regulated by specific patterns of action potential firing, with an emphasis on new information on epigenetic regulation of gene expression. Patterned action potential activity activates intracellular signaling networks selectively in accordance with the kinetics of activation and inactivation of second messengers, phosphorylation and dephosphorylation of protein kinases, and cytoplasmic and nuclear calcium dynamics, which differentially activate specific transcription factors. Increasing evidence also implicates activity-dependent regulation of epigenetic mechanisms to alter chromatin architecture. Changes in three-dimensional chromatin structure, including chromatin compaction, looping, double-stranded DNA breaks, histone and DNA modification, are altered by action potential activity to selectively inhibit or promote transcription of specific genes. These mechanisms of activity-dependent regulation of gene expression are important in neural development, plasticity, and in neurological and psychological disorders.

    更新日期:2018-08-30
  • LRRK2 Phosphorylation: Behind the Scenes
    Neuroscientist (IF 7.461) Pub Date : 2018-01-31
    Tina De Wit; Veerle Baekelandt; Evy Lobbestael

    Mutations in the gene encoding leucine-rich repeat kinase 2 (LRRK2) are known today as the most common genetic cause of Parkinson’s disease (PD). LRRK2 is a large protein that is hypothesized to regulate other proteins as a scaffold in downstream signaling pathways. This is supported by the multiple domain composition of LRRK2 with several protein-protein interaction domains combined with kinase and GTPase activity. LRRK2 is highly phosphorylated at sites that are strictly controlled by upstream regulators, including its own kinase domain. In cultured cells, most pathogenic mutants display increased autophosphorylation at S1292, but decreased phosphorylation at sites controlled by other kinases. We only begin to understand how LRRK2 phosphorylation is regulated and how this impacts its physiological and pathological function. Intriguingly, LRRK2 kinase inhibition, currently one of the most prevailing disease-modifying therapeutic strategies for PD, induces LRRK2 dephosphorylation at sites that are also dephosphorylated in pathogenic variants. In addition, LRRK2 kinase inhibition can induce LRRK2 protein degradation, which might be related to the observed inhibitor-induced adverse effects on the lung in rodents and non-human primates, as it resembles the lung pathology in LRRK2 knock-out animals. In this review, we will provide an overview of how LRRK2 phosphorylation is regulated and how this complex regulation relates to several molecular and cellular features of LRRK2.

    更新日期:2018-08-30
  • GABA—from Inhibition to Cognition: Emerging Concepts
    Neuroscientist (IF 7.461) Pub Date : 2017-10-12
    T. Schmidt-Wilcke; E. Fuchs; K. Funke; A. Vlachos; F. Müller-Dahlhaus; N. A. J. Puts; R. E. Harris; R. A. E. Edden

    Neural functioning and plasticity can be studied on different levels of organization and complexity ranging from the molecular and synaptic level to neural circuitry of whole brain networks. Across neuroscience different methods are being applied to better understand the role of various neurotransmitter systems in the evolution of perception and cognition. GABA is the main inhibitory neurotransmitter in the adult mammalian brain and, depending on the brain region, up to 25% of the total number of cortical neurons are GABAergic interneurons. At the one end of the spectrum, GABAergic neurons have been accurately described with regard to cell morphological, molecular, and electrophysiological properties; at the other end researchers try to link GABA concentrations in specific brain regions to human behavior using magnetic resonance spectroscopy. One of the main challenges of modern neuroscience currently is to integrate knowledge from highly specialized subfields at distinct biological scales into a coherent picture that bridges the gap between molecules and behavior. In the current review, recent findings from different fields of GABA research are summarized delineating a potential strategy to develop a more holistic picture of the function and role of GABA.

    更新日期:2018-08-30
  • Aging in the Brain: New Roles of Epigenetics in Cognitive Decline
    Neuroscientist (IF 7.461) Pub Date : 2018-06-07
    Jolie D. Barter; Thomas C. Foster

    Gene expression in the aging brain depends on transcription signals generated by senescent physiology, interacting with genetic and epigenetic programs. In turn, environmental factors influence epigenetic mechanisms, such that an epigenetic–environmental link may contribute to the accumulation of cellular damage, susceptibility or resilience to stressors, and variability in the trajectory of age-related cognitive decline. Epigenetic mechanisms, DNA methylation and histone modifications, alter chromatin structure and the accessibility of DNA. Furthermore, small non-coding RNA, termed microRNA (miRNA) bind to messenger RNA (mRNA) to regulate translation. In this review, we examine key questions concerning epigenetic mechanisms in regulating the expression of genes associated with brain aging and age-related cognitive decline. In addition, we highlight the interaction of epigenetics with senescent physiology and environmental factors in regulating transcription.

    更新日期:2018-08-30
  • Behavioral Manipulation by Optogenetics in the Nonhuman Primate
    Neuroscientist (IF 7.461) Pub Date : 2017-09-05
    Chunshan Deng; Hong Yuan; Ji Dai

    Given their neuroanatomical similarities to humans and their ability to perform complex behaviors, the nonhuman primate has been an important model for understanding complex systems such as sensory processing, motor control, social interaction, and nervous system disorders. Optogenetics offers cell-type specific neural control with millisecond precision, making it a powerful neural modulation technique. Combining optogenetics with the nonhuman primate model promises to lead to significant advances in both basic and applied research. In the past few years, optogenetics has made considerable progress in the nonhuman primate. Here, we systematically review the current state-of-art of optogenetics in the nonhuman primate with an emphasis on behavioral manipulation. Given its recent successes, we believe that the progress in the nonhuman primate will boost the translation of optogenetics to clinical applications in the near future.

    更新日期:2018-08-30
  • Glucocerebrosidase and Parkinson Disease: Molecular, Clinical, and Therapeutic Implications
    Neuroscientist (IF 7.461) Pub Date : 2018-02-04
    Roberta Balestrino; Anthony H. V. Schapira

    Parkinson disease (PD) is a complex neurodegenerative disease characterised by multiple motor and non-motor symptoms. In the last 20 years, more than 20 genes have been identified as causes of parkinsonism. Following the observation of higher risk of PD in patients affected by Gaucher disease, a lysosomal disorder caused by mutations in the glucocerebrosidase (GBA) gene, it was discovered that mutations in this gene constitute the single largest risk factor for development of idiopathic PD. Patients with PD and GBA mutations are clinically indistinguishable from patients with idiopathic PD, although some characteristics emerge depending on the specific mutation, such as slightly earlier onset. The molecular mechanisms which lead to this increased PD risk in GBA mutation carriers are multiple and not yet fully elucidated, they include alpha-synuclein aggregation, lysosomal-autophagy dysfunction and endoplasmic reticulum stress. Moreover, dysfunction of glucocerebrosidase has also been demonstrated in non-GBA PD, suggesting its interaction with other pathogenic mechanisms. Therefore, GBA enzyme function represents an interesting pharmacological target for PD. Cell and animal models suggest that increasing GBA enzyme activity can reduce alpha-synuclein levels. Clinical trials of ambroxol, a glucocerebrosidase chaperone, are currently ongoing in PD and PD dementia, as is a trial of substrate reduction therapy. The aim of this review is to summarise the main features of GBA-PD and discuss the implications of glucocerebrosidase modulation on PD pathogenesis.

    更新日期:2018-08-30
  • Exercise-Induced Neuroplasticity: A Mechanistic Model and Prospects for Promoting Plasticity
    Neuroscientist (IF 7.461) Pub Date : 2018-04-21
    Jenin El-Sayes; Diana Harasym; Claudia V. Turco; Mitchell B. Locke; Aimee J. Nelson

    Aerobic exercise improves cognitive and motor function by inducing neural changes detected using molecular, cellular, and systems level neuroscience techniques. This review unifies the knowledge gained across various neuroscience techniques to provide a comprehensive profile of the neural mechanisms that mediate exercise-induced neuroplasticity. Using a model of exercise-induced neuroplasticity, this review emphasizes the sequence of neural events that accompany exercise, and ultimately promote changes in human performance. This is achieved by differentiating between neuroplasticity induced by acute versus chronic aerobic exercise. Furthermore, this review emphasizes experimental considerations that influence the opportunity to observe exercise-induced neuroplasticity in humans. These include modifiable factors associated with the exercise intervention and nonmodifiable factors such as biological sex, ovarian hormones, genetic variations, and fitness level. To maximize the beneficial effects of exercise in health, disease, and following injury, future research should continue to explore the mechanisms that mediate exercise-induced neuroplasticity. This review identifies some fundamental gaps in knowledge that may serve to guide future research in this area.

    更新日期:2018-07-14
  • Noncoding RNAs and Stroke
    Neuroscientist (IF 7.461) Pub Date : 2018-04-11
    Xuejing Zhang; Milton H. Hamblin; Ke-Jie Yin

    Over many years, extensive efforts have focused on the development and improvement of diagnostic and therapeutic strategies to reduce stroke-associated neurovascular damage, such as blood-brain barrier dysfunction, brain edema, parenchymal inflammation, and neural cell death. However, the only clinically applied pharmacological therapy to date for the treatment of acute ischemic stroke is thrombolysis. Because of the short therapeutic window of current thrombolytic therapy and the activation of various pathophysiological signaling cascades triggered after ischemic stroke, the development of new therapies is urgently required. Noncoding RNAs (ncRNAs) are defined as untranslated regulatory RNA molecules. Although ncRNAs with biological roles have been known for almost 60 years, they have within the past decade emerged as key mediators of posttranscriptional gene expression/function in pathological aspects of ischemic stroke. With properties of relative stability, specificity, and reproducibility, ncRNAs are considered to be promising as biomarkers and better candidates than proteins and genes for early recognition of the onset of disease. In this update, we summarized the current knowledge for three groups of ncRNAs in stroke, focusing on the role of long noncoding RNAs and circular RNAs as biomarkers for stroke and as targets for regulating large sets of genes in related pathways after ischemic stroke.

    更新日期:2018-07-14
  • Dendritic Spine Elimination: Molecular Mechanisms and Implications
    Neuroscientist (IF 7.461) Pub Date : 2018-05-02
    Ivar S. Stein; Karen Zito

    Dynamic modification of synaptic connectivity in response to sensory experience is a vital step in the refinement of brain circuits as they are established during development and modified during learning. In addition to the well-established role for new spine growth and stabilization in the experience-dependent plasticity of neural circuits, dendritic spine elimination has been linked to improvements in learning, and dysregulation of spine elimination has been associated with intellectual disability and behavioral impairment. Proper brain function requires a tightly regulated balance between spine formation and spine elimination. Although most studies have focused on the mechanisms of spine formation, considerable progress has been made recently in delineating the neural activity patterns and downstream molecular mechanisms that drive dendritic spine elimination. Here, we review the current state of knowledge concerning the signaling pathways that drive dendritic spine shrinkage and elimination and we discuss their implication in neuropsychiatric and neurodegenerative disease.

    更新日期:2018-05-02
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.
化学 • 材料 期刊列表
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