Scholars@Duke
Josh Huang

Josh Huang

Duke School of Medicine Distinguished Professor in Neuroscience
Neurobiology
josh.huang@duke.edu
311 Research Drive, Box 3209, Durham, NC 27710
311 Research Drive, Box 3209, Durham, NC 27710
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Selected Publications

Axo-axonic synaptic input drives homeostatic plasticity by tuning the axon initial segment structurally and functionally.

Journal Article Sci Adv · August 2, 2024 Homeostatic plasticity maintains the stability of functional brain networks. The axon initial segment (AIS), where action potentials start, undergoes dynamic adjustment to exert powerful control over neuronal firing properties in response to network activi ... Full text Link to item Cite

Specific and comprehensive genetic targeting reveals brain-wide distribution and synaptic input patterns of GABAergic axo-axonic interneurons

Journal Article eLife · July 16, 2024 Axo-axonic cells (AACs), also called chandelier cells (ChCs) in the cerebral cortex, are the most distinctive type of GABAergic interneurons described in the neocortex, hippocampus, and basolateral amygdala (BLA). AACs selectively innervate glutama ... Full text Cite

Direct and indirect neurogenesis generate a mosaic of distinct glutamatergic projection neuron types in cerebral cortex.

Journal Article Neuron · August 16, 2023 Variations in size and complexity of the cerebral cortex result from differences in neuron number and composition, rooted in evolutionary changes in direct and indirect neurogenesis (dNG and iNG) that are mediated by radial glia and intermediate progenitor ... Full text Link to item Cite

The progenitor basis of cortical projection neuron diversity.

Journal Article Curr Opin Neurobiol · August 2023 Diverse glutamatergic projection neurons (PNs) mediate myriad processing streams and output channels of the cerebral cortex. Yet, how different types of neural progenitors, such as radial glia (RGs) and intermediate progenitors (IPs), produce PN diversity, ... Full text Link to item Cite

DSCAM gene triplication causes excessive GABAergic synapses in the neocortex in Down syndrome mouse models.

Journal Article PLoS Biol · April 2023 Down syndrome (DS) is caused by the trisomy of human chromosome 21 (HSA21). A major challenge in DS research is to identify the HSA21 genes that cause specific symptoms. Down syndrome cell adhesion molecule (DSCAM) is encoded by a HSA21 gene. Previous stud ... Full text Link to item Cite

Cortical glutamatergic projection neuron types contribute to distinct functional subnetworks.

Journal Article Nat Neurosci · March 2023 The cellular basis of cerebral cortex functional architecture remains not well understood. A major challenge is to monitor and decipher neural network dynamics across broad cortical areas yet with projection-neuron-type resolution in real time during behav ... Full text Link to item Cite

Programmable RNA sensing for cell monitoring and manipulation.

Journal Article Nature · October 2022 RNA is a central and universal mediator of genetic information underlying the diversity of cell types and cell states, which together shape tissue organization and organismal function across species and lifespans. Despite numerous advances in RNA sequencin ... Full text Link to item Cite

A genetically defined insula-brainstem circuit selectively controls motivational vigor.

Journal Article Cell · December 22, 2021 The anterior insular cortex (aIC) plays a critical role in cognitive and motivational control of behavior, but the underlying neural mechanism remains elusive. Here, we show that aIC neurons expressing Fezf2 (aICFezf2), which are the pyramidal tract neuron ... Full text Link to item Cite

Recruitment and inhibitory action of hippocampal axo-axonic cells during behavior.

Journal Article Neuron · December 1, 2021 The axon initial segment of hippocampal pyramidal cells is a key subcellular compartment for action potential generation, under GABAergic control by the "chandelier" or axo-axonic cells (AACs). Although AACs are the only cellular source of GABA targeting t ... Full text Link to item Cite

Morphological diversity of single neurons in molecularly defined cell types.

Journal Article Nature · October 2021 Dendritic and axonal morphology reflects the input and output of neurons and is a defining feature of neuronal types1,2, yet our knowledge of its diversity remains limited. Here, to systematically examine complete single-neuron morphologies on a brain-wide ... Full text Link to item Cite

Genetic dissection of the glutamatergic neuron system in cerebral cortex.

Journal Article Nature · October 2021 Diverse types of glutamatergic pyramidal neurons mediate the myriad processing streams and output channels of the cerebral cortex1,2, yet all derive from neural progenitors of the embryonic dorsal telencephalon3,4. Here we establish genetic strategies and ... Full text Link to item Cite

A multimodal cell census and atlas of the mammalian primary motor cortex.

Journal Article Nature · October 2021 Here we report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell trans ... Full text Link to item Cite

A transcriptomic and epigenomic cell atlas of the mouse primary motor cortex.

Journal Article Nature · October 2021 Single-cell transcriptomics can provide quantitative molecular signatures for large, unbiased samples of the diverse cell types in the brain1-3. With the proliferation of multi-omics datasets, a major challenge is to validate and integrate results into a b ... Full text Link to item Cite

Single-cell alternative polyadenylation analysis delineates GABAergic neuron types.

Journal Article BMC Biol · July 23, 2021 BACKGROUND: Alternative polyadenylation (APA) is emerging as an important mechanism in the post-transcriptional regulation of gene expression across eukaryotic species. Recent studies have shown that APA plays key roles in biological processes, such as cel ... Full text Link to item Cite

Retinal and Callosal Activity-Dependent Chandelier Cell Elimination Shapes Binocularity in Primary Visual Cortex.

Journal Article Neuron · February 3, 2021 In mammals with binocular vision, integration of the left and right visual scene relies on information in the center visual field, which are relayed from each retina in parallel and merge in the primary visual cortex (V1) through the convergence of ipsi- a ... Full text Link to item Cite

Axo-axonic synaptic input drives homeostatic plasticity by tuning the axon initial segment structurally and functionally.

Journal Article Sci Adv · August 2, 2024 Homeostatic plasticity maintains the stability of functional brain networks. The axon initial segment (AIS), where action potentials start, undergoes dynamic adjustment to exert powerful control over neuronal firing properties in response to network activi ... Full text Link to item Cite

Specific and comprehensive genetic targeting reveals brain-wide distribution and synaptic input patterns of GABAergic axo-axonic interneurons

Journal Article eLife · July 16, 2024 Axo-axonic cells (AACs), also called chandelier cells (ChCs) in the cerebral cortex, are the most distinctive type of GABAergic interneurons described in the neocortex, hippocampus, and basolateral amygdala (BLA). AACs selectively innervate glutama ... Full text Cite

Direct and indirect neurogenesis generate a mosaic of distinct glutamatergic projection neuron types in cerebral cortex.

Journal Article Neuron · August 16, 2023 Variations in size and complexity of the cerebral cortex result from differences in neuron number and composition, rooted in evolutionary changes in direct and indirect neurogenesis (dNG and iNG) that are mediated by radial glia and intermediate progenitor ... Full text Link to item Cite

The progenitor basis of cortical projection neuron diversity.

Journal Article Curr Opin Neurobiol · August 2023 Diverse glutamatergic projection neurons (PNs) mediate myriad processing streams and output channels of the cerebral cortex. Yet, how different types of neural progenitors, such as radial glia (RGs) and intermediate progenitors (IPs), produce PN diversity, ... Full text Link to item Cite

DSCAM gene triplication causes excessive GABAergic synapses in the neocortex in Down syndrome mouse models.

Journal Article PLoS Biol · April 2023 Down syndrome (DS) is caused by the trisomy of human chromosome 21 (HSA21). A major challenge in DS research is to identify the HSA21 genes that cause specific symptoms. Down syndrome cell adhesion molecule (DSCAM) is encoded by a HSA21 gene. Previous stud ... Full text Link to item Cite

Cortical glutamatergic projection neuron types contribute to distinct functional subnetworks.

Journal Article Nat Neurosci · March 2023 The cellular basis of cerebral cortex functional architecture remains not well understood. A major challenge is to monitor and decipher neural network dynamics across broad cortical areas yet with projection-neuron-type resolution in real time during behav ... Full text Link to item Cite

Programmable RNA sensing for cell monitoring and manipulation.

Journal Article Nature · October 2022 RNA is a central and universal mediator of genetic information underlying the diversity of cell types and cell states, which together shape tissue organization and organismal function across species and lifespans. Despite numerous advances in RNA sequencin ... Full text Link to item Cite

A genetically defined insula-brainstem circuit selectively controls motivational vigor.

Journal Article Cell · December 22, 2021 The anterior insular cortex (aIC) plays a critical role in cognitive and motivational control of behavior, but the underlying neural mechanism remains elusive. Here, we show that aIC neurons expressing Fezf2 (aICFezf2), which are the pyramidal tract neuron ... Full text Link to item Cite

Recruitment and inhibitory action of hippocampal axo-axonic cells during behavior.

Journal Article Neuron · December 1, 2021 The axon initial segment of hippocampal pyramidal cells is a key subcellular compartment for action potential generation, under GABAergic control by the "chandelier" or axo-axonic cells (AACs). Although AACs are the only cellular source of GABA targeting t ... Full text Link to item Cite

Morphological diversity of single neurons in molecularly defined cell types.

Journal Article Nature · October 2021 Dendritic and axonal morphology reflects the input and output of neurons and is a defining feature of neuronal types1,2, yet our knowledge of its diversity remains limited. Here, to systematically examine complete single-neuron morphologies on a brain-wide ... Full text Link to item Cite

Genetic dissection of the glutamatergic neuron system in cerebral cortex.

Journal Article Nature · October 2021 Diverse types of glutamatergic pyramidal neurons mediate the myriad processing streams and output channels of the cerebral cortex1,2, yet all derive from neural progenitors of the embryonic dorsal telencephalon3,4. Here we establish genetic strategies and ... Full text Link to item Cite

A multimodal cell census and atlas of the mammalian primary motor cortex.

Journal Article Nature · October 2021 Here we report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell trans ... Full text Link to item Cite

A transcriptomic and epigenomic cell atlas of the mouse primary motor cortex.

Journal Article Nature · October 2021 Single-cell transcriptomics can provide quantitative molecular signatures for large, unbiased samples of the diverse cell types in the brain1-3. With the proliferation of multi-omics datasets, a major challenge is to validate and integrate results into a b ... Full text Link to item Cite

Single-cell alternative polyadenylation analysis delineates GABAergic neuron types.

Journal Article BMC Biol · July 23, 2021 BACKGROUND: Alternative polyadenylation (APA) is emerging as an important mechanism in the post-transcriptional regulation of gene expression across eukaryotic species. Recent studies have shown that APA plays key roles in biological processes, such as cel ... Full text Link to item Cite

Retinal and Callosal Activity-Dependent Chandelier Cell Elimination Shapes Binocularity in Primary Visual Cortex.

Journal Article Neuron · February 3, 2021 In mammals with binocular vision, integration of the left and right visual scene relies on information in the center visual field, which are relayed from each retina in parallel and merge in the primary visual cortex (V1) through the convergence of ipsi- a ... Full text Link to item Cite

Cortical glutamatergic projection neuron types contribute to distinct functional subnetworks

Journal Article · 2021 The cellular basis of cerebral cortex functional architecture remains not well understood. A major challenge is to monitor and decipher neural network dynamics across broad cortical areas yet with projection neuron (PN)-type resolution in real time during ... Full text Cite

A Genetically Defined Compartmentalized Striatal Direct Pathway for Negative Reinforcement.

Journal Article Cell · October 1, 2020 The striosome compartment within the dorsal striatum has been implicated in reinforcement learning and regulation of motivation, but how striosomal neurons contribute to these functions remains elusive. Here, we show that a genetically identified striosoma ... Full text Link to item Cite

Genetic dissection of glutamatergic neuron subpopulations and developmental trajectories in the cerebral cortex

Journal Article · 2020 ABSTRACT Diverse types of glutamatergic pyramidal neurons (PyNs) mediate the myriad processing streams and output channels of the cerebral cortex, yet all derive from neural progenitors of the embryonic dorsal telencephalon. Here, we establish gen ... Full text Cite

Cellular Anatomy of the Mouse Primary Motor Cortex

Journal Article · 2020 An essential step toward understanding brain function is to establish a cellular-resolution structural framework upon which multi-scale and multi-modal information spanning molecules, cells, circuits and systems can be integrated and interpreted. Here, thr ... Full text Cite

A multimodal cell census and atlas of the mammalian primary motor cortex

Journal Article · 2020 ABSTRACT We report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex (MOp or M1) as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale anal ... Full text Cite

High-Throughput Mapping of Long-Range Neuronal Projection Using In Situ Sequencing.

Journal Article Cell · October 17, 2019 Understanding neural circuits requires deciphering interactions among myriad cell types defined by spatial organization, connectivity, gene expression, and other properties. Resolving these cell types requires both single-neuron resolution and high through ... Full text Link to item Cite

The diversity of GABAergic neurons and neural communication elements.

Journal Article Nat Rev Neurosci · September 2019 The phenotypic diversity of cortical GABAergic neurons is probably necessary for their functional versatility in shaping the spatiotemporal dynamics of neural circuit operations underlying cognition. Deciphering the logic of this diversity requires compreh ... Full text Link to item Cite

Genetic Single Neuron Anatomy Reveals Fine Granularity of Cortical Axo-Axonic Cells.

Journal Article Cell Rep · March 12, 2019 Parsing diverse nerve cells into biological types is necessary for understanding neural circuit organization. Morphology is an intuitive criterion for neuronal classification and a proxy of connectivity, but morphological diversity and variability often pr ... Full text Link to item Cite

Maternal experience-dependent cortical plasticity in mice is circuit- and stimulus-specific and requires MECP2

Journal Article · 2019 ABSTRACT The neurodevelopmental disorder Rett syndrome is caused by mutations in the gene Mecp2 . Misexpression of the protein MECP2 is thought to contribute to neuropathology by causing dysregulation of plasticity. Female heterozygous Mecp2 mutan ... Full text Cite

Mouse Cntnap2 and Human CNTNAP2 ASD Alleles Cell Autonomously Regulate PV+ Cortical Interneurons.

Journal Article Cereb Cortex · November 1, 2018 Human mutations in CNTNAP2 are associated with an array of neuropsychiatric and neurological syndromes, including speech and language disorders, epilepsy, and autism spectrum disorder (ASD). We examined Cntnap2's expression and function in GABAergic cortic ... Full text Link to item Cite

Single-cell RNA Sequencing of Fluorescently Labeled Mouse Neurons Using Manual Sorting and Double In Vitro Transcription with Absolute Counts Sequencing (DIVA-Seq).

Journal Article J Vis Exp · October 26, 2018 Single-cell RNA sequencing (RNA-seq) is now a widely implemented tool for assaying gene expression. Commercially available single-cell RNA-sequencing platforms process all input cells indiscriminately. Sometimes, fluorescence-activated cell sorting (FACS) ... Full text Link to item Cite

Radial Glial Lineage Progression and Differential Intermediate Progenitor Amplification Underlie Striatal Compartments and Circuit Organization.

Journal Article Neuron · July 25, 2018 The circuitry of the striatum is characterized by two organizational plans: the division into striosome and matrix compartments, thought to mediate evaluation and action, and the direct and indirect pathways, thought to promote or suppress behavior. The de ... Full text Link to item Cite

Genetic approaches to access cell types in mammalian nervous systems.

Journal Article Curr Opin Neurobiol · June 2018 Understanding brain circuit organization and function requires systematic dissection of its cellular components. With vast cell number and diversity, mammalian nervous systems present a daunting challenge for achieving specific and comprehensive cell type ... Full text Link to item Cite

Characterizing the replicability of cell types defined by single cell RNA-sequencing data using MetaNeighbor.

Journal Article Nat Commun · February 28, 2018 Single-cell RNA-sequencing (scRNA-seq) technology provides a new avenue to discover and characterize cell types; however, the experiment-specific technical biases and analytic variability inherent to current pipelines may undermine its replicability. Meta- ... Full text Link to item Cite

Selective inhibitory control of pyramidal neuron ensembles and cortical subnetworks by chandelier cells.

Journal Article Nat Neurosci · October 2017 The neocortex comprises multiple information processing streams mediated by subsets of glutamatergic pyramidal cells (PCs) that receive diverse inputs and project to distinct targets. How GABAergic interneurons regulate the segregation and communication am ... Full text Link to item Cite

Targeting cells with single vectors using multiple-feature Boolean logic.

Journal Article Nat Methods · July 2014 Precisely defining the roles of specific cell types is an intriguing frontier in the study of intact biological systems and has stimulated the rapid development of genetically encoded tools for observation and control. However, targeting these tools with a ... Full text Link to item Cite

Presynaptic inhibition of spinal sensory feedback ensures smooth movement.

Journal Article Nature · May 1, 2014 The precision of skilled movement depends on sensory feedback and its refinement by local inhibitory microcircuits. One specialized set of spinal GABAergic interneurons forms axo-axonic contacts with the central terminals of sensory afferents, exerting pre ... Full text Link to item Cite

A cortical circuit for gain control by behavioral state.

Journal Article Cell · March 13, 2014 The brain's response to sensory input is strikingly modulated by behavioral state. Notably, the visual response of mouse primary visual cortex (V1) is enhanced by locomotion, a tractable and accessible example of a time-locked change in cortical state. The ... Full text Link to item Cite

Genetic labeling of neurons in mouse brain.

Journal Article Cold Spring Harb Protoc · February 1, 2014 Mammalian central nervous systems consist of highly diverse types of neurons, which are the functional units of neural circuits. To understand the organization, assembly, and function of neural circuits, it is necessary to develop and to improve technologi ... Full text Link to item Cite

Cre-dependent adeno-associated virus preparation and delivery for labeling neurons in the mouse brain.

Journal Article Cold Spring Harb Protoc · February 1, 2014 Virus-mediated gene delivery is a powerful strategy for labeling and manipulating neurons in mammalian brains. A major drawback of this gene delivery method has been the lack of cell-type specificity. However, methods that combine Cre-knockin mice and Cre- ... Full text Link to item Cite

Cortical interneurons that specialize in disinhibitory control.

Journal Article Nature · November 28, 2013 In the mammalian cerebral cortex the diversity of interneuronal subtypes underlies a division of labour subserving distinct modes of inhibitory control. A unique mode of inhibitory control may be provided by inhibitory neurons that specifically suppress th ... Full text Link to item Cite

A disinhibitory circuit mediates motor integration in the somatosensory cortex.

Journal Article Nat Neurosci · November 2013 The influence of motor activity on sensory processing is crucial for perception and motor execution. However, the underlying circuits are not known. To unravel the circuit by which activity in the primary vibrissal motor cortex (vM1) modulates sensory proc ... Full text Link to item Cite

A cortico-hippocampal learning rule shapes inhibitory microcircuit activity to enhance hippocampal information flow.

Journal Article Neuron · September 18, 2013 How does coordinated activity between distinct brain regions implement a set of learning rules to sculpt information processing in a given neural circuit? Using interneuron cell-type-specific optical activation and pharmacogenetic silencing in vitro, we sh ... Full text Link to item Cite

Lineage-specific laminar organization of cortical GABAergic interneurons.

Journal Article Nat Neurosci · September 2013 In the cerebral cortex, pyramidal cells and interneurons are generated in distant germinal zones, and so the mechanisms that control their precise assembly into specific microcircuits remain an enigma. Here we report that cortical interneurons labeled at t ... Full text Link to item Cite

Inhibition of inhibition in visual cortex: the logic of connections between molecularly distinct interneurons.

Journal Article Nat Neurosci · August 2013 Cortical inhibitory neurons contact each other to form a network of inhibitory synaptic connections. Our knowledge of the connectivity pattern underlying this inhibitory network is, however, still incomplete. Here we describe a simple and complementary int ... Full text Link to item Cite

Genetic approaches to neural circuits in the mouse.

Journal Article Annu Rev Neurosci · July 8, 2013 To understand the organization and assembly of mammalian brain circuits, we need a comprehensive tool set that can address the challenges of cellular diversity, spatial complexity at synapse resolution, dynamic complexity of circuit operations, and multifa ... Full text Link to item Cite

Contrast dependence and differential contributions from somatostatin- and parvalbumin-expressing neurons to spatial integration in mouse V1.

Journal Article J Neurosci · July 3, 2013 A characteristic feature in the primary visual cortex is that visual responses are suppressed as a stimulus extends beyond the classical receptive field. Here, we examined the role of inhibitory neurons expressing somatostatin (SOM⁺) or parvalbumin (PV⁺) o ... Full text Link to item Cite

Distinct behavioural and network correlates of two interneuron types in prefrontal cortex.

Journal Article Nature · June 20, 2013 Neurons in the prefrontal cortex exhibit diverse behavioural correlates, an observation that has been attributed to cell-type diversity. To link identified neuron types with network and behavioural functions, we recorded from the two largest genetically de ... Full text Link to item Cite

SEMA3A signaling controls layer-specific interneuron branching in the cerebellum.

Journal Article Curr Biol · May 20, 2013 BACKGROUND: GABAergic interneurons regulate the balance and dynamics of neural circuits, in part, by elaborating their strategically placed axon branches that innervate specific cellular and subcellular targets. However, the molecular mechanisms that regul ... Full text Link to item Cite

Neural cell adhesion molecule-mediated Fyn activation promotes GABAergic synapse maturation in postnatal mouse cortex.

Journal Article J Neurosci · April 3, 2013 GABAergic basket interneurons form perisomatic synapses, which are essential for regulating neural networks, and their alterations are linked to various cognitive dysfunction. Maturation of basket synapses in postnatal cortex is activity dependent. In part ... Full text Link to item Cite

New insights into the classification and nomenclature of cortical GABAergic interneurons.

Journal Article Nat Rev Neurosci · March 2013 A systematic classification and accepted nomenclature of neuron types is much needed but is currently lacking. This article describes a possible taxonomical solution for classifying GABAergic interneurons of the cerebral cortex based on a novel, web-based ... Full text Link to item Cite

Experience-dependent modification of a central amygdala fear circuit.

Journal Article Nat Neurosci · March 2013 The amygdala is essential for fear learning and expression. The central amygdala (CeA), once viewed as a passive relay between the amygdala complex and downstream fear effectors, has emerged as an active participant in fear conditioning. However, the mecha ... Full text Link to item Cite

Role of glutamic acid decarboxylase 67 in regulating cortical parvalbumin and GABA membrane transporter 1 expression: implications for schizophrenia.

Journal Article Neurobiol Dis · February 2013 Markers of GABA neurotransmission are altered in multiple regions of the neocortex in individuals with schizophrenia. Lower levels of glutamic acid decarboxylase 67 (GAD67) mRNA and protein, which is responsible for most cortical GABA synthesis, are accomp ... Full text Link to item Cite

The spatial and temporal origin of chandelier cells in mouse neocortex.

Journal Article Science · January 4, 2013 Diverse γ-aminobutyric acid-releasing interneurons regulate the functional organization of cortical circuits and derive from multiple embryonic sources. It remains unclear to what extent embryonic origin influences interneuron specification and cortical in ... Full text Link to item Cite

A neural circuit for spatial summation in visual cortex.

Journal Article Nature · October 11, 2012 The response of cortical neurons to a sensory stimulus is modulated by the context. In the visual cortex, for example, stimulation of a pyramidal cell's receptive-field surround can attenuate the cell's response to a stimulus in the centre of its receptive ... Full text Link to item Cite

Neuronal circuitry mechanism regulating adult quiescent neural stem-cell fate decision.

Journal Article Nature · September 6, 2012 Adult neurogenesis arises from neural stem cells within specialized niches. Neuronal activity and experience, presumably acting on this local niche, regulate multiple stages of adult neurogenesis, from neural progenitor proliferation to new neuron maturati ... Full text Link to item Cite

Activation of specific interneurons improves V1 feature selectivity and visual perception.

Journal Article Nature · August 16, 2012 Inhibitory interneurons are essential components of the neural circuits underlying various brain functions. In the neocortex, a large diversity of GABA (γ-aminobutyric acid) interneurons has been identified on the basis of their morphology, molecular marke ... Full text Link to item Cite

Unique functional properties of somatostatin-expressing GABAergic neurons in mouse barrel cortex.

Journal Article Nat Neurosci · February 26, 2012 Neocortical GABAergic neurons have diverse molecular, structural and electrophysiological features, but the functional correlates of this diversity are largely unknown. We found unique membrane potential dynamics of somatostatin-expressing (SOM) neurons in ... Full text Link to item Cite

Cortical glutamic acid decarboxylase 67 deficiency results in lower cannabinoid 1 receptor messenger RNA expression: implications for schizophrenia.

Journal Article Biol Psychiatry · January 15, 2012 BACKGROUND: Levels of cannabinoid 1 receptor (CB1R) messenger RNA (mRNA) and protein, which are expressed most heavily in the cholecystokinin class of γ-aminobutyric acid (GABA) neurons, are lower in the dorsolateral prefrontal cortex in schizophrenia, and ... Full text Link to item Cite

GABA signaling promotes synapse elimination and axon pruning in developing cortical inhibitory interneurons.

Journal Article J Neurosci · January 4, 2012 Accumulating evidence indicates that GABA acts beyond inhibitory synaptic transmission and regulates the development of inhibitory synapses in the vertebrate brain, but the underlying cellular mechanism is not well understood. We have combined live imaging ... Full text Link to item Cite

Developmental Coordination of Gene Expression between Synaptic Partners During GABAergic Circuit Assembly in Cerebellar Cortex.

Journal Article Front Neural Circuits · 2012 The assembly of neural circuits involves multiple sequential steps such as the specification of cell-types, their migration to proper brain locations, morphological and physiological differentiation, and the formation and maturation of synaptic connections ... Full text Link to item Cite

Presynaptic GABA(B) Receptor Regulates Activity-Dependent Maturation and Patterning of Inhibitory Synapses through Dynamic Allocation of Synaptic Vesicles.

Journal Article Front Cell Neurosci · 2012 Accumulating evidence indicate that GABA regulates activity-dependent development of inhibitory synapses in the vertebrate brain, but the underlying mechanisms remain unclear. Here we combined live imaging of cortical GABAergic axons with single cell genet ... Full text Link to item Cite

Following the genes: a framework for animal modeling of psychiatric disorders.

Journal Article BMC Biol · November 11, 2011 The number of individual cases of psychiatric disorders that can be ascribed to identified, rare, single mutations is increasing with great rapidity. Such mutations can be recapitulated in mice to generate animal models with direct etiological validity. De ... Full text Link to item Cite

A resource of Cre driver lines for genetic targeting of GABAergic neurons in cerebral cortex.

Journal Article Neuron · September 22, 2011 A key obstacle to understanding neural circuits in the cerebral cortex is that of unraveling the diversity of GABAergic interneurons. This diversity poses general questions for neural circuit analysis: how are these interneuron cell types generated and ass ... Full text Link to item Cite

Distinct maturation profiles of perisomatic and dendritic targeting GABAergic interneurons in the mouse primary visual cortex during the critical period of ocular dominance plasticity.

Journal Article J Neurophysiol · August 2011 In the rodent primary visual cortex, maturation of GABA inhibitory circuitry is regulated by visual input and contributes to the onset and progression of ocular dominance (OD) plasticity. Cortical inhibitory circuitry consists of diverse groups of GABAergi ... Full text Link to item Cite

Cortical representations of olfactory input by trans-synaptic tracing.

Journal Article Nature · April 14, 2011 In the mouse, each class of olfactory receptor neurons expressing a given odorant receptor has convergent axonal projections to two specific glomeruli in the olfactory bulb, thereby creating an odour map. However, it is unclear how this map is represented ... Full text Link to item Cite

Differential dynamics and activity-dependent regulation of alpha- and beta-neurexins at developing GABAergic synapses.

Journal Article Proc Natl Acad Sci U S A · December 28, 2010 Neurexins (NRXs) and neuroligins are key synaptic adhesion molecules that also recruit synaptic signaling machineries. Neurexins consist of α- and β-isoforms, but how they couple synaptic transmission and adhesion to regulate activity-dependent synapse dev ... Full text Link to item Cite

Visual representations by cortical somatostatin inhibitory neurons--selective but with weak and delayed responses.

Journal Article J Neurosci · October 27, 2010 Somatostatin-expressing inhibitory (SOM) neurons in the sensory cortex consist mostly of Martinotti cells, which project ascending axons to layer 1. Due to their sparse distribution, the representational properties of these neurons remain largely unknown. ... Full text Link to item Cite

Response features of parvalbumin-expressing interneurons suggest precise roles for subtypes of inhibition in visual cortex.

Journal Article Neuron · September 9, 2010 Inhibitory interneurons in the cerebral cortex include a vast array of subtypes, varying in their molecular signatures, electrophysiological properties, and connectivity patterns. This diversity suggests that individual inhibitory classes have unique roles ... Full text Link to item Cite

Maturation of GABAergic inhibition promotes strengthening of temporally coherent inputs among convergent pathways.

Journal Article PLoS Comput Biol · June 3, 2010 Spike-timing-dependent plasticity (STDP), a form of Hebbian plasticity, is inherently stabilizing. Whether and how GABAergic inhibition influences STDP is not well understood. Using a model neuron driven by converging inputs modifiable by STDP, we determin ... Full text Link to item Cite

Activity-dependent development of inhibitory synapses and innervation pattern: role of GABA signalling and beyond.

Journal Article J Physiol · May 1, 2009 GABA-mediated synaptic inhibition is crucial in neural circuit operations. The development of GABAergic inhibitory synapses and innervation pattern in mammalian neocortex is a prolonged process, extending well into the postnatal period, and is regulated by ... Full text Link to item Cite

A proposal for a coordinated effort for the determination of brainwide neuroanatomical connectivity in model organisms at a mesoscopic scale.

Journal Article PLoS Comput Biol · March 2009 In this era of complete genomes, our knowledge of neuroanatomical circuitry remains surprisingly sparse. Such knowledge is critical, however, for both basic and clinical research into brain function. Here we advocate for a concerted effort to fill this gap ... Full text Link to item Cite

Transient neurites of retinal horizontal cells exhibit columnar tiling via homotypic interactions.

Journal Article Nat Neurosci · January 2009 Sensory neurons with common functions are often nonrandomly arranged and form dendritic territories that show little overlap, or tiling. Repulsive homotypic interactions underlie such patterns in cell organization in invertebrate neurons. It is unclear how ... Full text Link to item Cite

Differential activity-dependent, homeostatic plasticity of two neocortical inhibitory circuits.

Journal Article J Neurophysiol · October 2008 Chronic changes in neuronal activity homeostatically regulate excitatory circuitry. However, little is known about how activity regulates inhibitory circuits or specific inhibitory neuron types. Here, we examined the activity-dependent regulation of two ne ... Full text Link to item Cite

Bergmann glia and the recognition molecule CHL1 organize GABAergic axons and direct innervation of Purkinje cell dendrites.

Journal Article PLoS Biol · April 29, 2008 The geometric and subcellular organization of axon arbors distributes and regulates electrical signaling in neurons and networks, but the underlying mechanisms have remained elusive. In rodent cerebellar cortex, stellate interneurons elaborate characterist ... Full text Link to item Cite

High-resolution labeling and functional manipulation of specific neuron types in mouse brain by Cre-activated viral gene expression.

Journal Article PLoS One · April 16, 2008 We describe a method that combines Cre-recombinase knockin mice and viral-mediated gene transfer to genetically label and functionally manipulate specific neuron types in the mouse brain. We engineered adeno-associated viruses (AAVs) that express GFP, dsRe ... Full text Link to item Cite

Robust but delayed thalamocortical activation of dendritic-targeting inhibitory interneurons.

Journal Article Proc Natl Acad Sci U S A · February 12, 2008 GABA-releasing cortical interneurons are crucial for the neural transformations underlying sensory perception, providing "feedforward" inhibition that constrains the temporal window for synaptic integration. To mediate feedforward inhibition, inhibitory in ... Full text Link to item Cite

GABA and neuroligin signaling: linking synaptic activity and adhesion in inhibitory synapse development.

Journal Article Curr Opin Neurobiol · February 2008 GABA-mediated synaptic inhibition is crucial in neural circuit operations. In mammalian brains, the development of inhibitory synapses and innervation patterns is often a prolonged postnatal process, regulated by neural activity. Emerging evidence indicate ... Full text Link to item Cite

Activity-dependent PSA expression regulates inhibitory maturation and onset of critical period plasticity.

Journal Article Nat Neurosci · December 2007 Functional maturation of GABAergic innervation in the developing visual cortex is regulated by neural activity and sensory inputs and in turn influences the critical period of ocular dominance plasticity. Here we show that polysialic acid (PSA), presented ... Full text Link to item Cite

Development of GABA innervation in the cerebral and cerebellar cortices.

Journal Article Nat Rev Neurosci · September 2007 In many areas of the vertebrate brain, such as the cerebral and cerebellar cortices, neural circuits rely on inhibition mediated by GABA (gamma-aminobutyric acid) to shape the spatiotemporal patterns of electrical signalling. The richness and subtlety of i ... Full text Link to item Cite

GAD67-mediated GABA synthesis and signaling regulate inhibitory synaptic innervation in the visual cortex.

Journal Article Neuron · June 21, 2007 The development of GABAergic inhibitory circuits is shaped by neural activity, but the underlying mechanisms are unclear. Here, we demonstrate a novel function of GABA in regulating GABAergic innervation in the adolescent brain, when GABA is mainly known a ... Full text Link to item Cite

Correlation between axonal morphologies and synaptic input kinetics of interneurons from mouse visual cortex.

Journal Article Cereb Cortex · January 2007 Neocortical interneurons display great morphological and physiological variability and are ideally positioned to control circuit dynamics, although their exact role is still poorly understood. To better understand this diversity, we have performed a detail ... Full text Link to item Cite

Cytosolic branched chain aminotransferase (BCATc) mRNA is up-regulated in restricted brain areas of BDNF transgenic mice.

Journal Article Brain Res · September 7, 2006 Branched chain aminotransferase (BCAT) catalyzes the transamination of the essential branched chain amino acids (leucine, isoleucine and valine) with alpha-ketoglutarate. BCAT exists in two isoforms: one cytosolic (BCATc), mainly expressed in the nervous s ... Full text Link to item Cite

GABAB receptor isoforms caught in action at the scene.

Journal Article Neuron · May 18, 2006 The metabotropic GABAB receptors mediate slow synaptic inhibition and consist of heterodimers of GABAB1 and GABAB2 subunits. The only known molecular diversity of the GABAB receptors arises from the two GABAB1 isoforms, but its functional significance has ... Full text Link to item Cite

Subcellular organization of GABAergic synapses: role of ankyrins and L1 cell adhesion molecules.

Journal Article Nat Neurosci · February 2006 In vertebrate nervous systems, different classes of synaptic inputs are often segregated into restricted compartments of target neurons. For example, distinct types of GABAergic interneurons preferentially innervate subcellular domains and have been implic ... Full text Link to item Cite

Molecular taxonomy of major neuronal classes in the adult mouse forebrain.

Journal Article Nat Neurosci · January 2006 Identifying the neuronal cell types that comprise the mammalian forebrain is a central unsolved problem in neuroscience. Global gene expression profiles offer a potentially unbiased way to assess functional relationships between neurons. Here, we carried o ... Full text Link to item Cite

Maturation of GABAergic transmission and the timing of plasticity in visual cortex.

Journal Article Brain Res Brain Res Rev · December 1, 2005 During a brief postnatal critical period, excitatory connections in visual cortex can be easily modified by alterations of visual experience. Recent studies conducted in rodents, and particularly in genetically altered mice, have implicated the maturation ... Full text Link to item Cite

Specific functions of synaptically localized potassium channels in synaptic transmission at the neocortical GABAergic fast-spiking cell synapse.

Journal Article J Neurosci · May 25, 2005 Potassium (K+) channel subunits of the Kv3 subfamily (Kv3.1-Kv3.4) display a positively shifted voltage dependence of activation and fast activation/deactivation kinetics when compared with other voltage-gated K+ channels, features that confer on Kv3 chann ... Full text Link to item Cite

Neural cell adhesion molecule-secreting transgenic mice display abnormalities in GABAergic interneurons and alterations in behavior.

Journal Article J Neurosci · May 4, 2005 The extracellular region of the transmembrane neural cell adhesion molecule (NCAM-EC) is shed as a soluble fragment at elevated levels in the schizophrenic brain. A novel transgenic mouse line was generated to identify consequences on cortical development ... Full text Link to item Cite

Subcellular domain-restricted GABAergic innervation in primary visual cortex in the absence of sensory and thalamic inputs.

Journal Article Nat Neurosci · November 2004 Distinct classes of GABAergic synapses target restricted subcellular domains, thereby differentially regulating the input, integration and output of principal neurons, but the underlying mechanism for such synapse segregation is unclear. Here we show that ... Full text Link to item Cite

Experience and activity-dependent maturation of perisomatic GABAergic innervation in primary visual cortex during a postnatal critical period.

Journal Article J Neurosci · October 27, 2004 The neocortical GABAergic network consists of diverse interneuron cell types that display distinct physiological properties and target their innervations to subcellular compartments of principal neurons. Inhibition directed toward the soma and proximal den ... Full text Link to item Cite

Ankyrin-based subcellular gradient of neurofascin, an immunoglobulin family protein, directs GABAergic innervation at purkinje axon initial segment.

Journal Article Cell · October 15, 2004 Distinct classes of GABAergic synapses are segregated into subcellular domains (i.e., dendrite, soma, and axon initial segment-AIS), thereby differentially regulating the input, integration, and output of principal neurons. In cerebellum, for example, bask ... Full text Link to item Cite

Visual cortex is rescued from the effects of dark rearing by overexpression of BDNF.

Journal Article Proc Natl Acad Sci U S A · October 14, 2003 Visual deprivation such as dark rearing (DR) prolongs the critical period for ocular dominance plasticity and retards the maturation of gamma-aminobutyric acid (GABA)ergic inhibition in visual cortex. The molecular signals that mediate the effects of DR on ... Full text Link to item Cite

Brain-derived neurotrophic factor overexpression induces precocious critical period in mouse visual cortex.

Journal Article J Neurosci · November 15, 1999 Brain-derived neurotrophic factor (BDNF) is a candidate molecule for regulating activity-dependent synaptic plasticity on the grounds of its expression pattern in developing visual cortex and that of its receptor, trkB (Castr¿n et al., 1992; Bozzi et al., ... Full text Link to item Cite

BDNF regulates the maturation of inhibition and the critical period of plasticity in mouse visual cortex.

Journal Article Cell · September 17, 1999 Maturation of the visual cortex is influenced by visual experience during an early postnatal period. The factors that regulate such a critical period remain unclear. We examined the maturation and plasticity of the visual cortex in transgenic mice in which ... Full text Link to item Cite

PER protein interactions and temperature compensation of a circadian clock in Drosophila.

Journal Article Science · February 24, 1995 The periods of circadian clocks are relatively temperature-insensitive. Indeed, the perL mutation in the Drosophila melanogaster period gene, a central component of the clock, affects temperature compensation as well as period length. The per protein (PER) ... Full text Link to item Cite

Temporally regulated nuclear entry of the Drosophila period protein contributes to the circadian clock.

Journal Article Neuron · February 1995 The Drosophila period protein (PER) is a predominantly nuclear protein and a likely component of a circadian clock. PER is required for daily oscillations in the transcription of its own gene and thus participates in a circadian feedback loop. In this stud ... Full text Link to item Cite

PAS is a dimerization domain common to Drosophila period and several transcription factors.

Journal Article Nature · July 15, 1993 Mutations in the period gene product (PER) can shorten or lengthen the circadian rhythms of Drosophila melanogaster, but its biochemical activity has not been established. PER contains a motif of approximately 270 amino acids whose function is unknown (ter ... Full text Link to item Cite

The strength and periodicity of D. melanogaster circadian rhythms are differentially affected by alterations in period gene expression.

Journal Article Neuron · May 1991 The per gene of D. melanogaster influences or participates in the generation of biological rhythms. Previous experiments have identified the head as the location from which per exerts its effect on circadian rhythms. To localize further this region and to ... Full text Link to item Cite

Neuronal mechanisms underlying behavioral switching in a pteropod mollusc

Journal Article Journal of Comparative Physiology A · April 1, 1990 In the pteropod mollusc Clione limacina, wing retraction takes precedence over spontaneous and continuous swimming, a phenomenon here defined as behavioral switching. The wing retraction system is organized as a simple reflex in which wing mechanoreceptors ... Full text Cite

Smooth muscle fiber types and a novel pattern of thick filaments in the wing of the pteropod mollusc Clione limacina

Journal Article Cell and Tissue Research · January 1, 1989 Wing (parapodial) retraction in the pteropod mollusc Clione limacina is a reflex triggered by tactile stimulation. Light and transmission electron microscopy revealed three groups of smooth muscles in the wing hemocoel that participate in retraction moveme ... Full text Cite