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  • Decision making: Making hasty decisions
    Nat. Rev. Neurosci. (IF 28.88) Pub Date : 2017-09-07
    Katherine Whalley

    The activity of neurons in the basal ganglia contributes to the weighting of speed versus accuracy, rather than to deliberation, in a motor decision-making task.

    更新日期:2017-09-19
  • Reward: Restraint from risky reward
    Nat. Rev. Neurosci. (IF 28.88) Pub Date : 2017-09-07
    Natasha Bray

    In mice, a set of projections from the medial prefrontal cortex to the nucleus accumbens suppress reward seeking under risky conditions.

    更新日期:2017-09-19
  • Non-coding RNA: Regulatory circles
    Nat. Rev. Neurosci. (IF 28.88) Pub Date : 2017-09-19
    Darran Yates

    In mice, the circular RNA Cdr1as regulates microRNA expression in the brain and sensorimotor gating.

    更新日期:2017-09-19
  • Reward: Eating goes down a treat
    Nat. Rev. Neurosci. (IF 28.88) Pub Date : 2017-09-07
    Natasha Bray

    A study in mice identified neurons in the central amygdala that express the serotonin 2A receptor and positively reinforce the consumption of food.

    更新日期:2017-09-19
  • Neurodegenerative disease: Towards transplant therapy
    Nat. Rev. Neurosci. (IF 28.88) Pub Date : 2017-09-19
    Natasha Bray

    The long-term safety and efficacy of using induced pluripotent stem cell (iPSC)-derived neurons to replace midbrain dopaminergic neurons lost in Parkinson disease (PD) have not been tested in primates. Kikuchi et al. grafted human iPSC-derived midbrain dopaminergic progenitors into the putamen of macaques that

    更新日期:2017-09-19
  • Learning and memory: Memories take the sub-way
    Nat. Rev. Neurosci. (IF 28.88) Pub Date : 2017-09-19
    Sian Lewis

    Two pathways from CA1 to the entorhinal cortex — a direct pathway and an indirect pathway, that projects via the hippocampal subiculum — are shown to play dissociable roles in memory formation and retrieval, respectively.

    更新日期:2017-09-19
  • Visual processing: Face off
    Nat. Rev. Neurosci. (IF 28.88) Pub Date : 2017-09-19
    Natasha Bray

    How face patches — areas of cortex that process visual faces — develop is not known. Livingstone and colleagues reared three macaques for ∼200 days without any visual exposure to faces and used functional MRI to measure neural responses to images of faces, objects and

    更新日期:2017-09-19
  • Techniques: Having a field day
    Nat. Rev. Neurosci. (IF 28.88) Pub Date : 2017-09-19
    Natasha Bray

    Recording magnetic fields associated with neuronal activity could have certain advantages over voltage recordings, but current probes to detect such fields are too large for in vivo use. Caruso et al. developed micron-scale 'magnetrodes' and used these in the cat visual cortex to

    更新日期:2017-09-19
  • Neurodevelopmental disorders: A transcription-targeting target
    Nat. Rev. Neurosci. (IF 28.88) Pub Date : 2017-09-19
    Natasha Bray

    Fragile X mental retardation protein (FMRP) represses the transcription of many target genes, including genes that encode chromatin-associated proteins. Loss of FMRP leads to fragile X syndrome (FXS); however, whether misregulation of chromatin-associated proteins contributes to FXS is unclear. Korb et al. showed that

    更新日期:2017-09-19
  • The use of brain organoids to investigate neural development and disease
    Nat. Rev. Neurosci. (IF 28.88) Pub Date : 2017-09-07
    Elizabeth Di Lullo, Arnold R. Kriegstein

    Understanding the development and dysfunction of the human brain is a major goal of neurobiology. Much of our current understanding of human brain development has been derived from the examination of post-mortem and pathological specimens, bolstered by observations of developing non-human primates and experimental studies focused largely on mouse models. However, these tissue specimens and model systems cannot fully capture the unique and dynamic features of human brain development. Recent advances in stem cell technologies that enable the generation of human brain organoids from pluripotent stem cells (PSCs) promise to profoundly change our understanding of the development of the human brain and enable a detailed study of the pathogenesis of inherited and acquired brain diseases.

    更新日期:2017-09-19
  • The impact of cytoskeletal organization on the local regulation of neuronal transport
    Nat. Rev. Neurosci. (IF 28.88) Pub Date : 2017-08-31
    Jeffrey J. Nirschl, Amy E. Ghiretti, Erika L. F. Holzbaur

    Neurons are akin to modern cities in that both are dependent on robust transport mechanisms. Like the best mass transit systems, trafficking in neurons must be tailored to respond to local requirements. Neurons depend on both high-speed, long-distance transport and localized dynamics to correctly deliver cargoes and to tune synaptic responses. Here, we focus on the mechanisms that provide localized regulation of the transport machinery, including the cytoskeleton and molecular motors, to yield compartment-specific trafficking in the axon initial segment, axon terminal, dendrites and spines. The synthesis of these mechanisms provides a sophisticated and responsive transit system for the cell.

    更新日期:2017-09-19
  • Electrodiffusion phenomena in neuroscience: a neglected companion
    Nat. Rev. Neurosci. (IF 28.88) Pub Date : 2017-09-19
    Leonid P. Savtchenko, Mu Ming Poo, Dmitri A. Rusakov

    The emerging technological revolution in genetically encoded molecular sensors and super-resolution imaging provides neuroscientists with a pass to the real-time nano-world. On this small scale, however, classical principles of electrophysiology do not always apply. This is in large part because the nanoscopic heterogeneities in ionic concentrations and the local electric fields associated with individual ions and their movement can no longer be ignored. Here, we review basic principles of molecular electrodiffusion in the cellular environment of organized brain tissue. We argue that accurate interpretation of physiological observations on the nanoscale requires a better understanding of the underlying electrodiffusion phenomena.

    更新日期:2017-09-19
  • Polyglutamine spinocerebellar ataxias — from genes to potential treatments
    Nat. Rev. Neurosci. (IF 28.88) Pub Date : 2017-08-17
    Henry L. Paulson, Vikram G. Shakkottai, H. Brent Clark, Harry T. Orr

    The dominantly inherited spinocerebellar ataxias (SCAs) are a large and diverse group of neurodegenerative diseases. The most prevalent SCAs (SCA1, SCA2, SCA3, SCA6 and SCA7) are caused by expansion of a glutamine-encoding CAG repeat in the affected gene. These SCAs represent a substantial portion of the polyglutamine neurodegenerative disorders and provide insight into this class of diseases as a whole. Recent years have seen considerable progress in deciphering the clinical, pathological, physiological and molecular aspects of the polyglutamine SCAs, with these advances establishing a solid base from which to pursue potential therapeutic approaches.

    更新日期:2017-09-19
  • Noncoding RNAs in neurodegeneration
    Nat. Rev. Neurosci. (IF 28.88) Pub Date : 2017-08-17
    Evgenia Salta, Bart De Strooper

    The emerging complexity of the transcriptional landscape poses great challenges to our conventional preconceptions of how the genome regulates brain function and dysfunction. Non-protein-coding RNAs (ncRNAs) confer a high level of intricate and dynamic regulation of various molecular processes in the CNS and they have been implicated in neurodevelopment and brain ageing, as well as in synapse function and cognitive performance, in both health and disease. ncRNA-mediated processes may be involved in various aspects of the pathogenesis of neurodegenerative disorders. Understanding these events may help to develop novel diagnostic and therapeutic tools. Here, we provide an overview of the complex mechanisms that are affected by the diverse ncRNA classes that have been implicated in neurodegeneration.

    更新日期:2017-09-19
  • Learning and memory: Memories take the sub-way
    Nat. Rev. Neurosci. (IF 28.88) Pub Date : 
    Sian Lewis

    Learning and memory: Memories take the sub-way Nature Reviews Neuroscience, Published online: 19 September 2017; doi:10.1038/nrn.2017.117 Two pathways from CA1 to the entorhinal cortex — a direct pathway and an indirect pathway, that projects via the hippocampal subiculum — are shown to play dissociable roles in memory formation and retrieval, respectively.

    更新日期:2017-09-19
  • Visual processing: Face off
    Nat. Rev. Neurosci. (IF 28.88) Pub Date : 
    Natasha Bray

    Visual processing: Face off Nature Reviews Neuroscience, Published online: 19 September 2017; doi:10.1038/nrn.2017.121

    更新日期:2017-09-19
  • Neurodevelopmental disorders: A transcription-targeting target
    Nat. Rev. Neurosci. (IF 28.88) Pub Date : 
    Natasha Bray

    Neurodevelopmental disorders: A transcription-targeting target Nature Reviews Neuroscience, Published online: 19 September 2017; doi:10.1038/nrn.2017.123

    更新日期:2017-09-19
  • Neurodegenerative disease: Towards transplant therapy
    Nat. Rev. Neurosci. (IF 28.88) Pub Date : 
    Natasha Bray

    Neurodegenerative disease: Towards transplant therapy Nature Reviews Neuroscience, Published online: 19 September 2017; doi:10.1038/nrn.2017.120

    更新日期:2017-09-19
  • Non-coding RNA: Regulatory circles
    Nat. Rev. Neurosci. (IF 28.88) Pub Date : 
    Darran Yates

    Non-coding RNA: Regulatory circles Nature Reviews Neuroscience, Published online: 19 September 2017; doi:10.1038/nrn.2017.118 In mice, the circular RNA Cdr1as regulates microRNA expression in the brain and sensorimotor gating.

    更新日期:2017-09-19
  • Techniques: Having a field day
    Nat. Rev. Neurosci. (IF 28.88) Pub Date : 
    Natasha Bray

    Techniques: Having a field day Nature Reviews Neuroscience, Published online: 19 September 2017; doi:10.1038/nrn.2017.122

    更新日期:2017-09-19
  • Electrodiffusion phenomena in neuroscience: a neglected companion
    Nat. Rev. Neurosci. (IF 28.88) Pub Date : 
    Leonid P. Savtchenko, Mu Ming Poo, Dmitri A. Rusakov

    The emerging technological revolution in genetically encoded molecular sensors and super-resolution imaging provides neuroscientists with a pass to the real-time nano-world. On this small scale, however, classical principles of electrophysiology do not always apply. This is in large part because the nanoscopic heterogeneities in ionic concentrations and the local electric fields associated with individual ions and their movement can no longer be ignored. Here, we review basic principles of molecular electrodiffusion in the cellular environment of organized brain tissue. We argue that accurate interpretation of physiological observations on the nanoscale requires a better understanding of the underlying electrodiffusion phenomena.

    更新日期:2017-09-19
  • Reward: Restraint from risky reward
    Nat. Rev. Neurosci. (IF 28.88) Pub Date : 2017-09-07
    Natasha Bray

    Reward: Restraint from risky reward Nature Reviews Neuroscience, Published online: 7 September 2017; doi:10.1038/nrn.2017.114 In mice, a set of projections from the medial prefrontal cortex to the nucleus accumbens suppress reward seeking under risky conditions.

    更新日期:2017-09-08
  • Decision making: Making hasty decisions
    Nat. Rev. Neurosci. (IF 28.88) Pub Date : 2017-09-07
    Katherine Whalley

    Decision making: Making hasty decisions Nature Reviews Neuroscience, Published online: 7 September 2017; doi:10.1038/nrn.2017.116 The activity of neurons in the basal ganglia contributes to the weighting of speed versus accuracy, rather than to deliberation, in a motor decision-making task.

    更新日期:2017-09-08
  • The use of brain organoids to investigate neural development and disease
    Nat. Rev. Neurosci. (IF 28.88) Pub Date : 2017-09-07
    Elizabeth Di Lullo, Arnold R. Kriegstein

    Understanding the development and dysfunction of the human brain is a major goal of neurobiology. Much of our current understanding of human brain development has been derived from the examination of post-mortem and pathological specimens, bolstered by observations of developing non-human primates and experimental studies focused largely on mouse models. However, these tissue specimens and model systems cannot fully capture the unique and dynamic features of human brain development. Recent advances in stem cell technologies that enable the generation of human brain organoids from pluripotent stem cells (PSCs) promise to profoundly change our understanding of the development of the human brain and enable a detailed study of the pathogenesis of inherited and acquired brain diseases.

    更新日期:2017-09-08
  • Reward: Eating goes down a treat
    Nat. Rev. Neurosci. (IF 28.88) Pub Date : 2017-09-07
    Natasha Bray

    Reward: Eating goes down a treat Nature Reviews Neuroscience, Published online: 7 September 2017; doi:10.1038/nrn.2017.115 A study in mice identified neurons in the central amygdala that express the serotonin 2A receptor and positively reinforce the consumption of food.

    更新日期:2017-09-08
  • The impact of cytoskeletal organization on the local regulation of neuronal transport
    Nat. Rev. Neurosci. (IF 28.88) Pub Date : 2017-08-31
    Jeffrey J. Nirschl, Amy E. Ghiretti, Erika L. F. Holzbaur

    Neurons are akin to modern cities in that both are dependent on robust transport mechanisms. Like the best mass transit systems, trafficking in neurons must be tailored to respond to local requirements. Neurons depend on both high-speed, long-distance transport and localized dynamics to correctly deliver cargoes and to tune synaptic responses. Here, we focus on the mechanisms that provide localized regulation of the transport machinery, including the cytoskeleton and molecular motors, to yield compartment-specific trafficking in the axon initial segment, axon terminal, dendrites and spines. The synthesis of these mechanisms provides a sophisticated and responsive transit system for the cell.

    更新日期:2017-09-08
  • Motor systems: Mice get manual
    Nat. Rev. Neurosci. (IF 28.88) Pub Date : 
    Natasha Bray

    Motor systems: Mice get manual Nature Reviews Neuroscience, Published online: 21 August 2017; doi:10.1038/nrn.2017.108 Species-dependent regulation of plexin A1 signalling may underlie the elimination and retention of cortico–motor neuronal contacts in developing mice and in developing primates, respectively.

    更新日期:2017-09-08
  • Ageing: Setting the speed
    Nat. Rev. Neurosci. (IF 28.88) Pub Date : 
    Darran Yates

    Ageing: Setting the speed Nature Reviews Neuroscience, Published online: 21 August 2017; doi:10.1038/nrn.2017.109 Hypothalamic neural stem cells may be important regulators of the speed at which ageing proceeds in mice.

    更新日期:2017-09-08
  • Noncoding RNAs in neurodegeneration
    Nat. Rev. Neurosci. (IF 28.88) Pub Date : 2017-08-17
    Evgenia Salta, Bart De Strooper

    The emerging complexity of the transcriptional landscape poses great challenges to our conventional preconceptions of how the genome regulates brain function and dysfunction. Non-protein-coding RNAs (ncRNAs) confer a high level of intricate and dynamic regulation of various molecular processes in the CNS and they have been implicated in neurodevelopment and brain ageing, as well as in synapse function and cognitive performance, in both health and disease. ncRNA-mediated processes may be involved in various aspects of the pathogenesis of neurodegenerative disorders. Understanding these events may help to develop novel diagnostic and therapeutic tools. Here, we provide an overview of the complex mechanisms that are affected by the diverse ncRNA classes that have been implicated in neurodegeneration.

    更新日期:2017-09-08
  • Polyglutamine spinocerebellar ataxias — from genes to potential treatments
    Nat. Rev. Neurosci. (IF 28.88) Pub Date : 2017-08-17
    Henry L. Paulson, Vikram G. Shakkottai, H. Brent Clark, Harry T. Orr

    The dominantly inherited spinocerebellar ataxias (SCAs) are a large and diverse group of neurodegenerative diseases. The most prevalent SCAs (SCA1, SCA2, SCA3, SCA6 and SCA7) are caused by expansion of a glutamine-encoding CAG repeat in the affected gene. These SCAs represent a substantial portion of the polyglutamine neurodegenerative disorders and provide insight into this class of diseases as a whole. Recent years have seen considerable progress in deciphering the clinical, pathological, physiological and molecular aspects of the polyglutamine SCAs, with these advances establishing a solid base from which to pursue potential therapeutic approaches.

    更新日期:2017-09-06
  • Motor systems: Mice get manual
    Nat. Rev. Neurosci. (IF 28.88) Pub Date : 2017-08-21
    Natasha Bray

    Species-dependent regulation of plexin A1 signalling may underlie the elimination and retention of cortico–motor neuronal contacts in developing mice and in developing primates, respectively.

    更新日期:2017-08-21
  • Ageing: Setting the speed
    Nat. Rev. Neurosci. (IF 28.88) Pub Date : 2017-08-21
    Darran Yates

    Hypothalamic neural stem cells may be important regulators of the speed at which ageing proceeds in mice.

    更新日期:2017-08-21
  • Behavioural neuroscience: King of the castle
    Nat. Rev. Neurosci. (IF 28.88) Pub Date : 2017-08-03
    Sian Lewis

    The likelihood of winning a bout of competitive behaviour is increased by past wins, and the neural circuitry underlying this crucial determinant of social rank in a group of mice is identified as a projection from the mediodorsal thalamus to the dorsomedial prefrontal cortex.

    更新日期:2017-08-21
  • Sleep and memory: Spindles take charge
    Nat. Rev. Neurosci. (IF 28.88) Pub Date : 2017-07-27
    Katherine Whalley

    This study provides evidence for a role for the thalamus in the synchronization of brain rhythms that drive memory consolidation during sleep.

    更新日期:2017-08-21
  • Neurodegenerative disease: A programmed killer
    Nat. Rev. Neurosci. (IF 28.88) Pub Date : 2017-08-03
    Katherine Whalley

    Neuronal loss is a hallmark of Alzheimer disease (AD), but the mechanisms through which the neurons die are unclear. Here, the authors described evidence for the activation of necroptosis — a programmed form of necrosis that has been implicated in multiple sclerosis and amyotrophic lateral

    更新日期:2017-08-21
  • Neuronal networks: Individual arrangements
    Nat. Rev. Neurosci. (IF 28.88) Pub Date : 2017-08-03
    Katherine Whalley

    Functional connectivity analyses of group data have revealed several large-scale distributed brain networks, including the default network (DN), frontoparietal control network (FPN) and dorsal attention network (dATN); however, few studies have examined network organization within individual subjects. The authors performed multiple functional MRI scans in

    更新日期:2017-08-21
  • Gut–brain communication: Permitting pain
    Nat. Rev. Neurosci. (IF 28.88) Pub Date : 2017-08-03
    Katherine Whalley

    Neuropathic pain is a common adverse effect of chemotherapeutic agents, such as oxaliplatin. The authors here showed that antibiotic-mediated eradication of the gut microbiota protects mice against both oxaliplatin-induced inflammation in the dorsal root ganglia and mechanical hyperalgesia. The permissive effect of the gut microbiota

    更新日期:2017-08-21
  • Psychiatric disorders: Splitting depression apart
    Nat. Rev. Neurosci. (IF 28.88) Pub Date : 2017-07-27
    Natasha Bray

    Two major components of depression-like behaviour in mice — social avoidance and helplessness — are mediated by distinct circuits that include parvalbumin-expressing neurons in the ventral pallidum.

    更新日期:2017-08-21
  • Psychiatric disorders: Acute actions
    Nat. Rev. Neurosci. (IF 28.88) Pub Date : 2017-08-03
    Katherine Whalley

    Selective serotonin reuptake inhibitors (SSRIs) are commonly used antidepressants; however, their mechanism of action is elusive. The authors here show that activation of serotonin 5-HT1B receptors on cholecystokinin-expressing interneurons (CCK neurons) in the dentate gyrus underlies the effects of acute SSRI treatment on

    更新日期:2017-08-21
  • Animal models of α-synucleinopathy for Parkinson disease drug development
    Nat. Rev. Neurosci. (IF 28.88) Pub Date : 2017-07-13
    James B. Koprich, Lorraine V. Kalia, Jonathan M. Brotchie

    A major challenge in Parkinson disease (PD) will be to turn an emerging and expanding pipeline of novel disease-modifying candidate compounds into therapeutics. Novel targets need in vivo validation, and candidate therapeutics require appropriate preclinical platforms on which to define potential efficacy and target engagement before advancement to clinical development. We propose that α-synuclein (α-syn)-based mammalian models will be crucial for this process. Here, we review α-syn transgenic mouse models, viral vector models of α-syn overexpression and models of 'prion-like' spread of α-syn, and describe how each of these model types may contribute to PD drug discovery. We conclude by presenting our opinion on how to use a combination of these models through the late-stage preclinical, proof-of-principle investigation of novel therapeutics.

    更新日期:2017-08-21
  • Neuronal cell-type classification: challenges, opportunities and the path forward
    Nat. Rev. Neurosci. (IF 28.88) Pub Date : 2017-08-03
    Hongkui Zeng, Joshua R. Sanes

    Neurons have diverse molecular, morphological, connectional and functional properties. We believe that the only realistic way to manage this complexity — and thereby pave the way for understanding the structure, function and development of brain circuits — is to group neurons into types, which can then be analysed systematically and reproducibly. However, neuronal classification has been challenging both technically and conceptually. New high-throughput methods have created opportunities to address the technical challenges associated with neuronal classification by collecting comprehensive information about individual cells. Nonetheless, conceptual difficulties persist. Borrowing from the field of species taxonomy, we propose principles to be followed in the cell-type classification effort, including the incorporation of multiple, quantitative features as criteria, the use of discontinuous variation to define types and the creation of a hierarchical system to represent relationships between cells. We review the progress of classifying cell types in the retina and cerebral cortex and propose a staged approach for moving forward with a systematic cell-type classification in the nervous system.

    更新日期:2017-08-21
  • Prefrontal–hippocampal interactions in episodic memory
    Nat. Rev. Neurosci. (IF 28.88) Pub Date : 2017-06-29
    Howard Eichenbaum

    The roles of the hippocampus and prefrontal cortex (PFC) in memory processing — individually or in concert — are a major topic of interest in memory research. These brain areas have distinct and complementary roles in episodic memory, and their interactions are crucial for learning and remembering events. Considerable evidence indicates that the PFC and hippocampus become coupled via oscillatory synchrony that reflects bidirectional flow of information. Furthermore, newer studies have revealed specific mechanisms whereby neural representations in the PFC and hippocampus are mediated through direct connections or through intermediary regions. These findings suggest a model of how the hippocampus and PFC, along with their intermediaries, operate as a system that uses the current context of experience to retrieve relevant memories.

    更新日期:2017-08-21
  • A new look at domain specificity: insights from social neuroscience
    Nat. Rev. Neurosci. (IF 28.88) Pub Date : 2017-07-06
    Robert P. Spunt, Ralph Adolphs

    The concept of domain specificity — which suggests that some aspects of neural processing are specialized for particular types of stimuli — has been invoked to explain a range of cognitive phenomena, including language, face perception and theory of mind, and has been a hallmark

    更新日期:2017-08-21
  • Behavioural neuroscience: King of the castle
    Nat. Rev. Neurosci. (IF 28.88) Pub Date : 2017-08-03
    Sian Lewis

    The likelihood of winning a bout of competitive behaviour is increased by past wins, and the neural circuitry underlying this crucial determinant of social rank in a group of mice is identified as a projection from the mediodorsal thalamus to the dorsomedial prefrontal cortex.

    更新日期:2017-08-18
  • Neuronal cell-type classification: challenges, opportunities and the path forward
    Nat. Rev. Neurosci. (IF 28.88) Pub Date : 2017-08-03
    Hongkui Zeng, Joshua R. Sanes

    Neurons have diverse molecular, morphological, connectional and functional properties. We believe that the only realistic way to manage this complexity — and thereby pave the way for understanding the structure, function and development of brain circuits — is to group neurons into types, which can then be analysed systematically and reproducibly. However, neuronal classification has been challenging both technically and conceptually. New high-throughput methods have created opportunities to address the technical challenges associated with neuronal classification by collecting comprehensive information about individual cells. Nonetheless, conceptual difficulties persist. Borrowing from the field of species taxonomy, we propose principles to be followed in the cell-type classification effort, including the incorporation of multiple, quantitative features as criteria, the use of discontinuous variation to define types and the creation of a hierarchical system to represent relationships between cells. We review the progress of classifying cell types in the retina and cerebral cortex and propose a staged approach for moving forward with a systematic cell-type classification in the nervous system.

    更新日期:2017-08-18
  • Psychiatric disorders: Splitting depression apart
    Nat. Rev. Neurosci. (IF 28.88) Pub Date : 2017-07-27
    Natasha Bray

    Two major components of depression-like behaviour in mice — social avoidance and helplessness — are mediated by distinct circuits that include parvalbumin-expressing neurons in the ventral pallidum.

    更新日期:2017-08-18
  • Animal models of α-synucleinopathy for Parkinson disease drug development
    Nat. Rev. Neurosci. (IF 28.88) Pub Date : 2017-07-13
    James B. Koprich, Lorraine V. Kalia, Jonathan M. Brotchie

    A major challenge in Parkinson disease (PD) will be to turn an emerging and expanding pipeline of novel disease-modifying candidate compounds into therapeutics. Novel targets need in vivo validation, and candidate therapeutics require appropriate preclinical platforms on which to define potential efficacy and target engagement before advancement to clinical development. We propose that α-synuclein (α-syn)-based mammalian models will be crucial for this process. Here, we review α-syn transgenic mouse models, viral vector models of α-syn overexpression and models of 'prion-like' spread of α-syn, and describe how each of these model types may contribute to PD drug discovery. We conclude by presenting our opinion on how to use a combination of these models through the late-stage preclinical, proof-of-principle investigation of novel therapeutics.

    更新日期:2017-08-18
  • Sleep and memory: Spindles take charge
    Nat. Rev. Neurosci. (IF 28.88) Pub Date : 2017-07-27
    Katherine Whalley

    This study provides evidence for a role for the thalamus in the synchronization of brain rhythms that drive memory consolidation during sleep.

    更新日期:2017-08-18
  • A new look at domain specificity: insights from social neuroscience
    Nat. Rev. Neurosci. (IF 28.88) Pub Date : 2017-07-06
    Robert P. Spunt, Ralph Adolphs

    The idea that specialized cognitive processes or brain regions are devoted to particular cognitive functions — known as domain specificity — remains an area of substantial debate. Adolphs and Spunt outline the challenges in defining and assessing domain specificity and use social neuroscience findings to suggest a new approach.

    更新日期:2017-08-18
  • Prefrontal–hippocampal interactions in episodic memory
    Nat. Rev. Neurosci. (IF 28.88) Pub Date : 2017-06-29
    Howard Eichenbaum

    The roles of the hippocampus and prefrontal cortex (PFC) in memory processing — individually or in concert — are a major topic of interest in memory research. These brain areas have distinct and complementary roles in episodic memory, and their interactions are crucial for learning and remembering events. Considerable evidence indicates that the PFC and hippocampus become coupled via oscillatory synchrony that reflects bidirectional flow of information. Furthermore, newer studies have revealed specific mechanisms whereby neural representations in the PFC and hippocampus are mediated through direct connections or through intermediary regions. These findings suggest a model of how the hippocampus and PFC, along with their intermediaries, operate as a system that uses the current context of experience to retrieve relevant memories.

    更新日期:2017-08-18
  • Neural circuits: The influence of hunger
    Nat. Rev. Neurosci. (IF 28.88) Pub Date : 2017-07-19
    Darran Yates

    In mice, hypothalamic agouti-related peptide-expressing neurons modulate food-cue-associated insular cortex activity to influence behaviour.

    更新日期:2017-08-18
  • Psychiatric disorders: A sensitive window
    Nat. Rev. Neurosci. (IF 28.88) Pub Date : 2017-07-06
    Natasha Bray

    In mice, postnatal stress leads to long-lasting changes in transcription in the ventral tegmental area, sensitizing the brain to stress later in life.

    更新日期:2017-08-18
  • Gut-brain communication: Making contact
    Nat. Rev. Neurosci. (IF 28.88) Pub Date : 2017-07-13
    Katherine Whalley

    Enterochromaffin cells in the gut epithelium act as chemosensors and can modulate neural function in response to intestinal signals.

    更新日期:2017-08-18
  • Neuroimmunology: Mistaken identity
    Nat. Rev. Neurosci. (IF 28.88) Pub Date : 2017-07-06
    Sian Lewis

    Fragments of the protein α-synuclein, which accumulates in substantia nigra neurons in Parkinson disease, are expressed on the surface of these substantia nigra neurons and induce a form of autoimmunity that could account for the degeneration of these cells in the disease.

    更新日期:2017-08-18
  • Microglia: A protective population?
    Nat. Rev. Neurosci. (IF 28.88) Pub Date : 2017-06-29
    Katherine Whalley

    Disease progression in a mouse model of Alzheimer disease is associated with the appearance of a population of disease-associated microglia that can phagocytose amyloid-β.

    更新日期:2017-08-18
  • Sensory systems: Tasting the water
    Nat. Rev. Neurosci. (IF 28.88) Pub Date : 2017-06-29
    Sian Lewis

    Water in the external environment is detected by acid-sensing taste receptor cells via a carbonic anhydrase 4-mediated pH change.

    更新日期:2017-08-18
  • Neural development: Regional influence
    Nat. Rev. Neurosci. (IF 28.88) Pub Date : 2017-07-19
    Sian Lewis

    In mice, the ventricular–subventricular zone (V–SVZ) continuously produces neural stem cells (NSCs). Proopiomelanocortin-expressing (POMC+) neurons of the hypothalamus were found to project selectively to anterior ventral (AV) regions of the V–SVZ. Ablation of these neurons decreased NSC proliferation selectively in the AV V–SVZ,

    更新日期:2017-08-18
  • Learning and memory: Catching fear memories
    Nat. Rev. Neurosci. (IF 28.88) Pub Date : 2017-07-19
    Sian Lewis

    Memory traces of long-term auditory fear memories are stored in the auditory cortex. Perineuronal nets (PNNs) are stable components of the extracellular matrix that could potentially provide a scaffold for long-term synaptic plasticity. In a model of auditory fear conditioning, mRNAs encoding three lecticans —

    更新日期:2017-08-18
  • Neural circuits: Hanging in the balance
    Nat. Rev. Neurosci. (IF 28.88) Pub Date : 2017-07-19
    Sian Lewis

    Oxytocinergic (OXT) neurons in the paraventricular nucleus (PVN) project to tonically active dopaminergic (DA) neurons in the vental tegmental area (VTA) and reticular area of the substantia nigra (SN), both of which regulate reward-based behaviour via projections to the ventral striatum (vStr). Optogenetic stimulation of

    更新日期:2017-08-18
  • Neural coding: Face values
    Nat. Rev. Neurosci. (IF 28.88) Pub Date : 2017-06-22
    Natasha Bray

    Neurons in the 'face patch' system in macaques code features of realistic faces along various continuous axes.

    更新日期:2017-08-18
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.
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