scispace - formally typeset
Search or ask a question
Author

Z. Josh Huang

Bio: Z. Josh Huang is an academic researcher from Cold Spring Harbor Laboratory. The author has contributed to research in topics: GABAergic & Inhibitory postsynaptic potential. The author has an hindex of 56, co-authored 109 publications receiving 16622 citations. Previous affiliations of Z. Josh Huang include Massachusetts Institute of Technology & Duke University.


Papers
More filters
Journal ArticleDOI
22 Sep 2011-Neuron
TL;DR: Using genetic engineering in mice, approximately 20 Cre and inducible CreER knockin driver lines that reliably target major classes and lineages of GABAergic neurons are generated, thereby enabling a systematic and comprehensive analysis from cell fate specification, migration, and connectivity, to their functions in network dynamics and behavior.

1,655 citations

Journal ArticleDOI
17 Sep 1999-Cell
TL;DR: It is proposed that BDNF promotes the maturation of cortical inhibition during early postnatal life, thereby regulating the critical period for visual cortical plasticity.

1,187 citations

Journal ArticleDOI
TL;DR: This work describes a simple and complementary interaction scheme between three large, molecularly distinct interneuron populations in mouse visual cortex: parvalbumin-expressing interneurons strongly inhibit one another but provide little inhibition to other populations, while somatostatin-expresses avoid inhibiting one another yet strongly inhibit all other populations.
Abstract: 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 interaction scheme between three large, molecularly distinct interneuron populations in mouse visual cortex: parvalbumin-expressing interneurons strongly inhibit one another but provide little inhibition to other populations. In contrast, somatostatin-expressing interneurons avoid inhibiting one another yet strongly inhibit all other populations. Finally, vasoactive intestinal peptide-expressing interneurons preferentially inhibit somatostatin-expressing interneurons. This scheme occurs in supragranular and infragranular layers, suggesting that inhibitory networks operate similarly at the input and output of the visual cortex. Thus, as the specificity of connections between excitatory neurons forms the basis for the cortical canonical circuit, the scheme described here outlines a standard connectivity pattern among cortical inhibitory neurons.

1,180 citations

Journal ArticleDOI
06 Oct 2013-Nature
TL;DR: A class of interneurons that express vasoactive intestinal polypeptide (VIP) mediates disinhibitory control in multiple areas of neocortex and is recruited by reinforcement signals, revealing a specific cell type and microcircuit underlying disinhibited control in cortex and demonstrating that it is activated under specific behavioural conditions.
Abstract: 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 the firing of other inhibitory neurons. Such disinhibition could lead to the selective amplification of local processing and serve the important computational functions of gating and gain modulation. Although several interneuron populations are known to target other interneurons to varying degrees, little is known about interneurons specializing in disinhibition and their in vivo function. Here we show that a class of interneurons that express vasoactive intestinal polypeptide (VIP) mediates disinhibitory control in multiple areas of neocortex and is recruited by reinforcement signals. By combining optogenetic activation with single-cell recordings, we examined the functional role of VIP interneurons in awake mice, and investigated the underlying circuit mechanisms in vitro in auditory and medial prefrontal cortices. We identified a basic disinhibitory circuit module in which activation of VIP interneurons transiently suppresses primarily somatostatin- and a fraction of parvalbumin-expressing inhibitory interneurons that specialize in the control of the input and output of principal cells, respectively. During the performance of an auditory discrimination task, reinforcement signals (reward and punishment) strongly and uniformly activated VIP neurons in auditory cortex, and in turn VIP recruitment increased the gain of a functional subpopulation of principal neurons. These results reveal a specific cell type and microcircuit underlying disinhibitory control in cortex and demonstrate that it is activated under specific behavioural conditions.

986 citations

Journal ArticleDOI
13 Mar 2014-Cell
TL;DR: These findings establish a cortical circuit for the enhancement of visual response by locomotion and provide a potential common Circuit for the modulation of sensory processing by behavioral state.

841 citations


Cited by
More filters
Journal ArticleDOI
TL;DR: A set of Cre reporter mice with strong, ubiquitous expression of fluorescent proteins of different spectra is generated and enables direct visualization of fine dendritic structures and axonal projections of the labeled neurons, which is useful in mapping neuronal circuitry, imaging and tracking specific cell populations in vivo.
Abstract: The Cre/lox system is widely used in mice to achieve cell-type-specific gene expression. However, a strong and universally responding system to express genes under Cre control is still lacking. We have generated a set of Cre reporter mice with strong, ubiquitous expression of fluorescent proteins of different spectra. The robust native fluorescence of these reporters enables direct visualization of fine dendritic structures and axonal projections of the labeled neurons, which is useful in mapping neuronal circuitry, imaging and tracking specific cell populations in vivo. Using these reporters and a high-throughput in situ hybridization platform, we are systematically profiling Cre-directed gene expression throughout the mouse brain in several Cre-driver lines, including new Cre lines targeting different cell types in the cortex. Our expression data are displayed in a public online database to help researchers assess the utility of various Cre-driver lines for cell-type-specific genetic manipulation.

5,365 citations

Journal ArticleDOI
Ed S. Lein1, Michael Hawrylycz1, Nancy Ao2, Mikael Ayres1, Amy Bensinger1, Amy Bernard1, Andrew F. Boe1, Mark S. Boguski1, Mark S. Boguski3, Kevin S. Brockway1, Emi J. Byrnes1, Lin Chen1, Li Chen2, Tsuey-Ming Chen2, Mei Chi Chin1, Jimmy Chong1, Brian E. Crook1, Aneta Czaplinska2, Chinh Dang1, Suvro Datta1, Nick Dee1, Aimee L. Desaki1, Tsega Desta1, Ellen Diep1, Tim A. Dolbeare1, Matthew J. Donelan1, Hong-Wei Dong1, Jennifer G. Dougherty1, Ben J. Duncan1, Amanda Ebbert1, Gregor Eichele4, Lili K. Estin1, Casey Faber1, Benjamin A.C. Facer1, Rick Fields2, Shanna R. Fischer1, Tim P. Fliss1, Cliff Frensley1, Sabrina N. Gates1, Katie J. Glattfelder1, Kevin R. Halverson1, Matthew R. Hart1, John G. Hohmann1, Maureen P. Howell1, Darren P. Jeung1, Rebecca A. Johnson1, Patrick T. Karr1, Reena Kawal1, Jolene Kidney1, Rachel H. Knapik1, Chihchau L. Kuan1, James H. Lake1, Annabel R. Laramee1, Kirk D. Larsen1, Christopher Lau1, Tracy Lemon1, Agnes J. Liang2, Ying Liu2, Lon T. Luong1, Jesse Michaels1, Judith J. Morgan1, Rebecca J. Morgan1, Marty Mortrud1, Nerick Mosqueda1, Lydia Ng1, Randy Ng1, Geralyn J. Orta1, Caroline C. Overly1, Tu H. Pak1, Sheana Parry1, Sayan Dev Pathak1, Owen C. Pearson1, Ralph B. Puchalski1, Zackery L. Riley1, Hannah R. Rockett1, Stephen A. Rowland1, Joshua J. Royall1, Marcos J. Ruiz2, Nadia R. Sarno1, Katherine Schaffnit1, Nadiya V. Shapovalova1, Taz Sivisay1, Clifford R. Slaughterbeck1, Simon Smith1, Kimberly A. Smith1, Bryan I. Smith1, Andy J. Sodt1, Nick N. Stewart1, Kenda-Ruth Stumpf1, Susan M. Sunkin1, Madhavi Sutram1, Angelene Tam2, Carey D. Teemer1, Christina Thaller2, Carol L. Thompson1, Lee R. Varnam1, Axel Visel5, Axel Visel4, Ray M. Whitlock1, Paul Wohnoutka1, Crissa K. Wolkey1, Victoria Y. Wong1, Matthew J.A. Wood2, Murat B. Yaylaoglu2, Rob Young1, Brian L. Youngstrom1, Xu Feng Yuan1, Bin Zhang2, Theresa A. Zwingman1, Allan R. Jones1 
11 Jan 2007-Nature
TL;DR: An anatomically comprehensive digital atlas containing the expression patterns of ∼20,000 genes in the adult mouse brain is described, providing an open, primary data resource for a wide variety of further studies concerning brain organization and function.
Abstract: Molecular approaches to understanding the functional circuitry of the nervous system promise new insights into the relationship between genes, brain and behaviour. The cellular diversity of the brain necessitates a cellular resolution approach towards understanding the functional genomics of the nervous system. We describe here an anatomically comprehensive digital atlas containing the expression patterns of approximately 20,000 genes in the adult mouse brain. Data were generated using automated high-throughput procedures for in situ hybridization and data acquisition, and are publicly accessible online. Newly developed image-based informatics tools allow global genome-scale structural analysis and cross-correlation, as well as identification of regionally enriched genes. Unbiased fine-resolution analysis has identified highly specific cellular markers as well as extensive evidence of cellular heterogeneity not evident in classical neuroanatomical atlases. This highly standardized atlas provides an open, primary data resource for a wide variety of further studies concerning brain organization and function.

4,944 citations

Journal ArticleDOI
TL;DR: Neurotrophins regulate development, maintenance, and function of vertebrate nervous systems, and control synaptic function and synaptic plasticity, while continuing to modulate neuronal survival.
Abstract: Neurotrophins regulate development, maintenance, and function of vertebrate nervous systems. Neurotrophins activate two different classes of receptors, the Trk family of receptor tyrosine kinases and p75NTR, a member of the TNF receptor superfamily. Through these, neurotrophins activate many signaling pathways, including those mediated by ras and members of the cdc-42/ras/rho G protein families, and the MAP kinase, PI-3 kinase, and Jun kinase cascades. During development, limiting amounts of neurotrophins function as survival factors to ensure a match between the number of surviving neurons and the requirement for appropriate target innervation. They also regulate cell fate decisions, axon growth, dendrite pruning, the patterning of innervation and the expression of proteins crucial for normal neuronal function, such as neurotransmitters and ion channels. These proteins also regulate many aspects of neural function. In the mature nervous system, they control synaptic function and synaptic plasticity, while continuing to modulate neuronal survival.

3,968 citations

Journal ArticleDOI
TL;DR: These findings call into question the concept of a “glial” cell class as the gene profiles of astrocyte and oligodendrocytes are as dissimilar to each other as they are to neurons, for better understanding of neural development, function, and disease.
Abstract: Understanding the cell–cell interactions that control CNS development and function has long been limited by the lack of methods to cleanly separate neural cell types. Here we describe methods for the prospective isolation and purification of astrocytes, neurons, and oligodendrocytes from developing and mature mouse forebrain. We used FACS (fluorescent-activated cell sorting) to isolate astrocytes from transgenic mice that express enhanced green fluorescent protein (EGFP) under the control of an S100β promoter. Using Affymetrix GeneChip Arrays, we then created a transcriptome database of the expression levels of >20,000 genes by gene profiling these three main CNS neural cell types at various postnatal ages between postnatal day 1 (P1) and P30. This database provides a detailed global characterization and comparison of the genes expressed by acutely isolated astrocytes, neurons, and oligodendrocytes. We found that Aldh1L1 is a highly specific antigenic marker for astrocytes with a substantially broader pattern of astrocyte expression than the traditional astrocyte marker GFAP. Astrocytes were enriched in specific metabolic and lipid synthetic pathways, as well as the draper/Megf10 and Mertk/integrin αvβ5 phagocytic pathways suggesting that astrocytes are professional phagocytes. Our findings call into question the concept of a “glial” cell class as the gene profiles of astrocytes and oligodendrocytes are as dissimilar to each other as they are to neurons. This transcriptome database of acutely isolated purified astrocytes, neurons, and oligodendrocytes provides a resource to the neuroscience community by providing improved cell-type-specific markers and for better understanding of neural development, function, and disease.

2,838 citations

01 Jan 2010
TL;DR: In this paper, the authors describe a scenario where a group of people are attempting to find a solution to the problem of "finding the needle in a haystack" in the environment.
Abstract: 中枢神経系疾患の治療は正常細胞(ニューロン)の機能維持を目的とするが,脳血管障害のように機能障害の原因が細胞の死滅に基づくことは多い.一方,脳腫瘍の治療においては薬物療法や放射線療法といった腫瘍細胞の死滅を目標とするものが大きな位置を占める.いずれの場合にも,細胞死の機序を理解することは各種病態や治療法の理解のうえで重要である.現在のところ最も研究の進んでいる細胞死の型はアポトーシスである.そのなかで重要な位置を占めるミトコンドリアにおける反応および抗アポトーシス因子について概要を紹介する.

2,716 citations