Genetic approaches to neural circuits in the mouse.

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 multifaceted developmental processes rooted in the genome. Complementary to physics- and chemistry-based methods, genetic tools tap into intrinsic cellular and developmental mechanisms. Thus, they have the potential to achieve appropriate spatiotemporal resolution and the cellular-molecular specificity necessary for observing and probing the makings and inner workings of neurons and neuronal circuits. Furthermore, genetic analysis will be key to unraveling the intricate link from genes to circuits to systems, in part through systematic targeting and tracking of individual cellular components of neural circuits. Here we review recent progress in genetic tool development and advances in genetic analysis of neural circuits in the mouse. We also discuss future directions and implications for understanding brain disorders.

[1]  S. Benzer BEHAVIORAL MUTANTS OF Drosophila ISOLATED BY COUNTERCURRENT DISTRIBUTION. , 1967, Proceedings of the National Academy of Sciences of the United States of America.

[2]  S. Benzer,et al.  Genetic dissection of the Drosophila nervous system by means of mosaics. , 1970, Proceedings of the National Academy of Sciences of the United States of America.

[3]  S. Brenner The genetics of Caenorhabditis elegans. , 1974, Genetics.

[4]  C. Nüsslein-Volhard,et al.  Mutations affecting segment number and polarity in Drosophila , 1980, Nature.

[5]  F. Ruddle,et al.  Integration and stable germ line transmission of genes injected into mouse pronuclei. , 1981, Science.

[6]  R. Palmiter,et al.  Somatic expression of herpes thymidine kinase in mice following injection of a fusion gene into eggs , 1981, Cell.

[7]  F. Costantini,et al.  Introduction of a rabbit β-globin gene into the mouse germ line , 1981, Nature.

[8]  M. Capecchi,et al.  Site-directed mutagenesis by gene targeting in mouse embryo-derived stem cells , 1987, Cell.

[9]  David W. Melton,et al.  Targetted correction of a mutant HPRT gene in mouse embryonic stem cells , 1987, Nature.

[10]  L. Hartwell,et al.  Twenty-five years of cell cycle genetics. , 1991, Genetics.

[11]  Alcino J. Silva,et al.  Deficient hippocampal long-term potentiation in alpha-calcium-calmodulin kinase II mutant mice. , 1992, Science.

[12]  M. Chalfie,et al.  Green fluorescent protein as a marker for gene expression. , 1994, Science.

[13]  M. Jasin,et al.  Targeted transgenesis. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[14]  Richard Axel,et al.  Visualizing an Olfactory Sensory Map , 1996, Cell.

[15]  David J. Anderson,et al.  Subregion- and Cell Type–Restricted Gene Knockout in Mouse Brain , 1996, Cell.

[16]  A. Bird,et al.  The methyl-CpG binding protein MeCP2 is essential for embryonic development in the mouse , 1996, Nature Genetics.

[17]  P Chambon,et al.  Regulation of Cre recombinase activity by mutated estrogen receptor ligand-binding domains. , 1997, Biochemical and biophysical research communications.

[18]  N. L. Chamberlin,et al.  Recombinant adeno-associated virus vector: use for transgene expression and anterograde tract tracing in the CNS , 1998, Brain Research.

[19]  Gero Miesenböck,et al.  Visualizing secretion and synaptic transmission with pH-sensitive green fluorescent proteins , 1998, Nature.

[20]  G. Feng,et al.  Imaging Neuronal Subsets in Transgenic Mice Expressing Multiple Spectral Variants of GFP , 2000, Neuron.

[21]  R. Axel,et al.  Genetic Ablation and Restoration of the Olfactory Topographic Map , 2000, Cell.

[22]  K. Kissa,et al.  Preferential transduction of neurons by canine adenovirus vectors and their efficient retrograde transport in vivo , 2001, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[23]  Y. Barde,et al.  Neurotrophins are required for nerve growth during development , 2001, Nature Neuroscience.

[24]  F. J. Livesey,et al.  Vertebrate neural cell-fate determination: Lessons from the retina , 2001, Nature Reviews Neuroscience.

[25]  U. Greferath,et al.  Visualization of functionally activated circuitry in the brain , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[26]  Vincenzo De Paola,et al.  AMPA receptors regulate dynamic equilibrium of presynaptic terminals in mature hippocampal networks , 2003, Nature Neuroscience.

[27]  J. Sanes,et al.  Watching the neuromuscular junction , 2003, Journal of neurocytology.

[28]  Dai Watanabe,et al.  Reversible Suppression of Glutamatergic Neurotransmission of Cerebellar Granule Cells In Vivo by Genetically Manipulated Expression of Tetanus Neurotoxin Light Chain , 2003, The Journal of Neuroscience.

[29]  T. Lemberger,et al.  α Complementation in the Cre recombinase enzyme , 2003 .

[30]  Shiaoching Gong,et al.  A gene expression atlas of the central nervous system based on bacterial artificial chromosomes , 2003, Nature.

[31]  E. Bamberg,et al.  Channelrhodopsin-2, a directly light-gated cation-selective membrane channel , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[32]  Winfried Denk,et al.  Neurons arise in the basal neuroepithelium of the early mammalian telencephalon: a major site of neurogenesis. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[33]  Matt Wachowiak,et al.  In Vivo Imaging of Neuronal Activity by Targeted Expression of a Genetically Encoded Probe in the Mouse , 2004, Neuron.

[34]  A. Kriegstein,et al.  Cortical neurons arise in symmetric and asymmetric division zones and migrate through specific phases , 2004, Nature Neuroscience.

[35]  E. Kremer,et al.  Long‐term in vivo transduction of neurons throughout the rat central nervous system using novel helper‐dependent CAV‐2 vectors , 2004, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[36]  Richard C Gerkin,et al.  Alteration of Neuronal Firing Properties after In Vivo Experience in a FosGFP Transgenic Mouse , 2004, The Journal of Neuroscience.

[37]  W. Hillen,et al.  Gene regulation by tetracyclines. , 2003, Genetic engineering.

[38]  H. Markram,et al.  Correlation maps allow neuronal electrical properties to be predicted from single-cell gene expression profiles in rat neocortex. , 2004, Cerebral cortex.

[39]  K. Deisseroth,et al.  Millisecond-timescale, genetically targeted optical control of neural activity , 2005, Nature Neuroscience.

[40]  Paola Arlotta,et al.  Neuronal Subtype-Specific Genes that Control Corticospinal Motor Neuron Development In Vivo , 2005, Neuron.

[41]  R. Palmiter,et al.  NPY/AgRP Neurons Are Essential for Feeding in Adult Mice but Can Be Ablated in Neonates , 2005, Science.

[42]  Matt Wachowiak,et al.  Odorant Representations Are Modulated by Intra- but Not Interglomerular Presynaptic Inhibition of Olfactory Sensory Neurons , 2005, Neuron.

[43]  Thorsten Buch,et al.  Agouti-related peptide–expressing neurons are mandatory for feeding , 2005, Nature Neuroscience.

[44]  R. Awatramani,et al.  Ligand‐activated Flpe for temporally regulated gene modifications , 2005, Genesis.

[45]  Steffen Jung,et al.  A Cre-inducible diphtheria toxin receptor mediates cell lineage ablation after toxin administration , 2005, Nature Methods.

[46]  William J Tyler,et al.  Synaptic vesicle recycling studied in transgenic mice expressing synaptopHluorin , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[47]  Susumu Tonegawa,et al.  In Vivo Two-Photon Imaging Reveals a Role of Arc in Enhancing Orientation Specificity in Visual Cortex , 2006, Cell.

[48]  Karel Svoboda,et al.  Rapid Redistribution of Synaptic PSD-95 in the Neocortex In Vivo , 2006, PLoS biology.

[49]  Samuel D. Gale,et al.  Cre recombinase-mediated restoration of nigrostriatal dopamine in dopamine-deficient mice reverses hypophagia and bradykinesia. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[50]  E. Callaway,et al.  Selective and Quickly Reversible Inactivation of Mammalian Neurons In Vivo Using the Drosophila Allatostatin Receptor , 2006, Neuron.

[51]  A. Joyner,et al.  Genetic inducible fate mapping in mouse: Establishing genetic lineages and defining genetic neuroanatomy in the nervous system , 2006, Developmental dynamics : an official publication of the American Association of Anatomists.

[52]  S. Nelson,et al.  Molecular taxonomy of major neuronal classes in the adult mouse forebrain , 2006, Nature Neuroscience.

[53]  Alan M. Moses,et al.  In vivo enhancer analysis of human conserved non-coding sequences , 2006, Nature.

[54]  Mark Mayford,et al.  Localization of a Stable Neural Correlate of Associative Memory , 2007, Science.

[55]  Ian R. Wickersham,et al.  Monosynaptic Restriction of Transsynaptic Tracing from Single, Genetically Targeted Neurons , 2007, Neuron.

[56]  R. W. Draft,et al.  Transgenic strategies for combinatorial expression of fluorescent proteins in the nervous system , 2007, Nature.

[57]  Allan R. Jones,et al.  Genome-wide atlas of gene expression in the adult mouse brain , 2007, Nature.

[58]  K. Svoboda,et al.  Channelrhodopsin-2–assisted circuit mapping of long-range callosal projections , 2007, Nature Neuroscience.

[59]  Charles R. Gerfen,et al.  Targeting Cre Recombinase to Specific Neuron Populations with Bacterial Artificial Chromosome Constructs , 2007, The Journal of Neuroscience.

[60]  T. Gingeras,et al.  Genome-wide transcription and the implications for genomic organization , 2007, Nature Reviews Genetics.

[61]  J. C. Kim,et al.  Molecular Neuroanatomy's “Three Gs”: A Primer , 2007, Neuron.

[62]  Masakatsu Watanabe,et al.  Fast manipulation of cellular cAMP level by light in vivo , 2007, Nature Methods.

[63]  B. Roth,et al.  Evolving the lock to fit the key to create a family of G protein-coupled receptors potently activated by an inert ligand , 2007, Proceedings of the National Academy of Sciences.

[64]  David J. Anderson,et al.  Reversible Silencing of Neuronal Excitability in Behaving Mice by a Genetically Targeted, Ivermectin-Gated Cl− Channel , 2007, Neuron.

[65]  J. Wess,et al.  Engineering GPCR signaling pathways with RASSLs , 2008, Nature Methods.

[66]  Atsushi Miyawaki,et al.  Tracing the silhouette of individual cells in S/G2/M phases with fluorescence. , 2008, Chemistry & biology.

[67]  K. Svoboda,et al.  Genetic Dissection of Neural Circuits , 2008, Neuron.

[68]  Susumu Tonegawa,et al.  Transgenic Inhibition of Synaptic Transmission Reveals Role of CA3 Output in Hippocampal Learning , 2008, Science.

[69]  D. Saur,et al.  A Cre-loxP-based mouse model for conditional somatic gene expression and knockdown in vivo by using avian retroviral vectors , 2008, Proceedings of the National Academy of Sciences.

[70]  Paul Pavlidis,et al.  Altered brain microRNA biogenesis contributes to phenotypic deficits in a 22q11-deletion mouse model , 2008, Nature Genetics.

[71]  G. Barnea,et al.  The genetic design of signaling cascades to record receptor activation , 2008, Proceedings of the National Academy of Sciences.

[72]  Benjamin R Arenkiel,et al.  Genetic control of neuronal activity in mice conditionally expressing TRPV1 , 2008, Nature Methods.

[73]  E. Deneris,et al.  Redefining the serotonergic system by genetic lineage , 2008, Nature Neuroscience.

[74]  M. Mank,et al.  Genetically encoded calcium indicators. , 2008, Chemical reviews.

[75]  Cori Bargmann,et al.  GFP Reconstitution Across Synaptic Partners (GRASP) Defines Cell Contacts and Synapses in Living Nervous Systems , 2008, Neuron.

[76]  Jeremy Nathans,et al.  Genetically-Directed, Cell Type-Specific Sparse Labeling for the Analysis of Neuronal Morphology , 2008, PloS one.

[77]  E. Callaway Transneuronal circuit tracing with neurotropic viruses , 2008, Current Opinion in Neurobiology.

[78]  P. Greengard,et al.  A Translational Profiling Approach for the Molecular Characterization of CNS Cell Types , 2008, Cell.

[79]  S. Sternson,et al.  A FLEX Switch Targets Channelrhodopsin-2 to Multiple Cell Types for Imaging and Long-Range Circuit Mapping , 2008, The Journal of Neuroscience.

[80]  Z. J. Huang,et al.  High-Resolution Labeling and Functional Manipulation of Specific Neuron Types in Mouse Brain by Cre-Activated Viral Gene Expression , 2008, PloS one.

[81]  Hongkui Zeng,et al.  An Inducible and Reversible Mouse Genetic Rescue System , 2008, PLoS genetics.

[82]  J. Sanes,et al.  Molecular identification of a retinal cell type that responds to upward motion , 2008, Nature.

[83]  Susana Q. Lima,et al.  PINP: A New Method of Tagging Neuronal Populations for Identification during In Vivo Electrophysiological Recording , 2009, PloS one.

[84]  E. Kuramoto,et al.  Two types of thalamocortical projections from the motor thalamic nuclei of the rat: a single neuron-tracing study using viral vectors. , 2009, Cerebral cortex.

[85]  Jeremy D. Schmahmann,et al.  A Proposal for a Coordinated Effort for the Determination of Brainwide Neuroanatomical Connectivity in Model Organisms at a Mesoscopic Scale , 2009, PLoS Comput. Biol..

[86]  R. Sprengel,et al.  Split-Cre Complementation Indicates Coincident Activity of Different Genes In Vivo , 2009, PloS one.

[87]  K. Svoboda,et al.  Experience-dependent structural synaptic plasticity in the mammalian brain , 2009, Nature Reviews Neuroscience.

[88]  Sreekanth H. Chalasani,et al.  Imaging neural activity in worms, flies and mice with improved GCaMP calcium indicators , 2009, Nature Methods.

[89]  C. Englund,et al.  Intermediate neuronal progenitors (basal progenitors) produce pyramidal-projection neurons for all layers of cerebral cortex. , 2009, Cerebral cortex.

[90]  A. Visel,et al.  ChIP-seq accurately predicts tissue-specific activity of enhancers , 2009, Nature.

[91]  M. Häusser,et al.  Electrophysiology in the age of light , 2009, Nature.

[92]  Raag D. Airan,et al.  Temporally precise in vivo control of intracellular signalling , 2009, Nature.

[93]  R. Palmiter,et al.  Cell-type-specific isolation of ribosome-associated mRNA from complex tissues , 2009, Proceedings of the National Academy of Sciences.

[94]  K. Svoboda,et al.  The subcellular organization of neocortical excitatory connections , 2009, Nature.

[95]  S. Shi,et al.  Specific synapses develop preferentially among sister excitatory neurons in the neocortex , 2009, Nature.

[96]  Frank Buchholz,et al.  Dre recombinase, like Cre, is a highly efficient site-specific recombinase in E. coli, mammalian cells and mice , 2009, Disease Models & Mechanisms.

[97]  A. Visel,et al.  Genomic Views of Distant-Acting Enhancers , 2009, Nature.

[98]  Nathaniel D Heintzman,et al.  Finding distal regulatory elements in the human genome. , 2009, Current opinion in genetics & development.

[99]  J. C. Kim,et al.  Genetic fate-mapping approaches: new means to explore the embryonic origins of the cochlear nucleus. , 2009, Methods in molecular biology.

[100]  K. Svoboda,et al.  Neural Activity in Barrel Cortex Underlying Vibrissa-Based Object Localization in Mice , 2010, Neuron.

[101]  C. Petersen,et al.  Membrane Potential Dynamics of GABAergic Neurons in the Barrel Cortex of Behaving Mice , 2010, Neuron.

[102]  Ian R. Wickersham,et al.  Monosynaptic circuit tracing in vivo through Cre-dependent targeting and complementation of modified rabies virus , 2010, Proceedings of the National Academy of Sciences.

[103]  G. Miyoshi,et al.  Genetic Fate Mapping Reveals That the Caudal Ganglionic Eminence Produces a Large and Diverse Population of Superficial Cortical Interneurons , 2010, The Journal of Neuroscience.

[104]  Walther Akemann,et al.  Imaging brain electric signals with genetically targeted voltage-sensitive fluorescent proteins , 2010, Nature Methods.

[105]  T. Wandless,et al.  A general chemical method to regulate protein stability in the mammalian central nervous system. , 2010, Chemistry & biology.

[106]  Dae-Shik Kim,et al.  Global and local fMRI signals driven by neurons defined optogenetically by type and wiring , 2010, Nature.

[107]  L. Luo,et al.  Genetic Mosaic Dissection of Lis1 and Ndel1 in Neuronal Migration , 2010, Neuron.

[108]  H. Monyer,et al.  In vivo evidence for the involvement of the carboxy terminal domain in assembling connexin 36 at the electrical synapse , 2010, Molecular and Cellular Neuroscience.

[109]  Lin Tian,et al.  Functional imaging of hippocampal place cells at cellular resolution during virtual navigation , 2010, Nature Neuroscience.

[110]  J. Gordon,et al.  Impaired hippocampal–prefrontal synchrony in a genetic mouse model of schizophrenia , 2010, Nature.

[111]  B. Zemelman,et al.  Two-photon single-cell optogenetic control of neuronal activity by sculpted light , 2010, Proceedings of the National Academy of Sciences.

[112]  Magdalena Götz,et al.  In vivo fate mapping and expression analysis reveals molecular hallmarks of prospectively isolated adult neural stem cells. , 2010, Cell stem cell.

[113]  K. Deisseroth,et al.  Molecular and Cellular Approaches for Diversifying and Extending Optogenetics , 2010, Cell.

[114]  E. Isacoff,et al.  Scanless two-photon excitation of channelrhodopsin-2 , 2010, Nature Methods.

[115]  Allan R. Jones,et al.  A robust and high-throughput Cre reporting and characterization system for the whole mouse brain , 2009, Nature Neuroscience.

[116]  Michael A. Henninger,et al.  High-Performance Genetically Targetable Optical Neural Silencing via Light-Driven Proton Pumps , 2010 .

[117]  S. Brenner Sequences and consequences , 2010, Philosophical Transactions of the Royal Society B: Biological Sciences.

[118]  Yongxin Zhao,et al.  An Expanded Palette of Genetically Encoded Ca2+ Indicators , 2011, Science.

[119]  T. Cutforth,et al.  Sensory maps in the olfactory cortex defined by long-range viral tracing of single neurons , 2011, Nature.

[120]  G. Feng,et al.  Shank3 mutant mice display autistic-like behaviours and striatal dysfunction , 2011, Nature.

[121]  B. Zemelman,et al.  The columnar and laminar organization of inhibitory connections to neocortical excitatory cells , 2010, Nature Neuroscience.

[122]  Andreas Buja,et al.  Dosage-dependent phenotypes in models of 16p11.2 lesions found in autism , 2011, Proceedings of the National Academy of Sciences.

[123]  David J. Anderson,et al.  A Cre-Dependent, Anterograde Transsynaptic Viral Tracer for Mapping Output Pathways of Genetically Marked Neurons , 2011, Neuron.

[124]  Nathan C. Klapoetke,et al.  A High-Light Sensitivity Optical Neural Silencer: Development and Application to Optogenetic Control of Non-Human Primate Cortex , 2010, Front. Syst. Neurosci..

[125]  Atsushi Miyawaki,et al.  Scale: a chemical approach for fluorescence imaging and reconstruction of transparent mouse brain , 2011, Nature Neuroscience.

[126]  Ericka B. Ramko,et al.  A Genetically Encoded Tag for Correlated Light and Electron Microscopy of Intact Cells, Tissues, and Organisms , 2011, PLoS biology.

[127]  Takeharu Nagai,et al.  Quantitative Comparison of Genetically Encoded Ca2+ Indicators in Cortical Pyramidal Cells and Cerebellar Purkinje Cells , 2011, Front. Cell. Neurosci..

[128]  James H. Marshel,et al.  New Rabies Virus Variants for Monitoring and Manipulating Activity and Gene Expression in Defined Neural Circuits , 2011, Neuron.

[129]  L. Enquist,et al.  Microdissection of neural networks by conditional reporter expression from a Brainbow herpesvirus , 2011, Proceedings of the National Academy of Sciences.

[130]  Andreas T. Schaefer,et al.  Two-photon calcium imaging of evoked activity from L5 somatosensory neurons in vivo , 2011, Nature Neuroscience.

[131]  Aljoscha Nern,et al.  Multiple new site-specific recombinases for use in manipulating animal genomes , 2011, Proceedings of the National Academy of Sciences.

[132]  Karl Deisseroth,et al.  Optogenetics in Neural Systems , 2011, Neuron.

[133]  Liqun Luo,et al.  Site-specific integrase-mediated transgenesis in mice via pronuclear injection , 2011, Proceedings of the National Academy of Sciences.

[134]  Russell S. Ray,et al.  Impaired Respiratory and Body Temperature Control Upon Acute Serotonergic Neuron Inhibition , 2011, Science.

[135]  Lief E. Fenno,et al.  The development and application of optogenetics. , 2011, Annual review of neuroscience.

[136]  Itamar Kahn,et al.  Characterization of the Functional MRI Response Temporal Linearity via Optical Control of Neocortical Pyramidal Neurons , 2011, The Journal of Neuroscience.

[137]  S. Anderson,et al.  Clonal Production and Organization of Inhibitory Interneurons in the Neocortex , 2011, Science.

[138]  G. Feng,et al.  Cell type–specific channelrhodopsin-2 transgenic mice for optogenetic dissection of neural circuitry function , 2011, Nature Methods.

[139]  W. Denk,et al.  The Big and the Small: Challenges of Imaging the Brain’s Circuits , 2011, Science.

[140]  D. Geschwind,et al.  Absence of CNTNAP2 Leads to Epilepsy, Neuronal Migration Abnormalities, and Core Autism-Related Deficits , 2011, Cell.

[141]  Kevin T. Beier,et al.  Anterograde or retrograde transsynaptic labeling of CNS neurons with vesicular stomatitis virus vectors , 2011, Proceedings of the National Academy of Sciences.

[142]  Ascl1 Genetics Reveals Insights into Cerebellum Local Circuit Assembly , 2011, The Journal of Neuroscience.

[143]  Z. J. Huang,et al.  Following the genes: a framework for animal modeling of psychiatric disorders , 2011, BMC Biology.

[144]  Ian R. Wickersham,et al.  Cortical representations of olfactory input by trans-synaptic tracing , 2011, Nature.

[145]  K. Mori,et al.  Continuous neurogenesis in the adult forebrain is required for innate olfactory responses , 2011, Proceedings of the National Academy of Sciences.

[146]  M. Groudine,et al.  Functional and Mechanistic Diversity of Distal Transcription Enhancers , 2011, Cell.

[147]  Hongkui Zeng,et al.  Differential tuning and population dynamics of excitatory and inhibitory neurons reflect differences in local intracortical connectivity , 2011, Nature Neuroscience.

[148]  S. Nelson,et al.  A Resource of Cre Driver Lines for Genetic Targeting of GABAergic Neurons in Cerebral Cortex , 2011, Neuron.

[149]  Adam E. Cohen,et al.  Electrical Spiking in Escherichia coli Probed with a Fluorescent Voltage-Indicating Protein , 2011, Science.

[150]  Allan R. Jones,et al.  Visual Tuning Properties of Genetically Identified Layer 2/3 Neuronal Types in the Primary Visual Cortex of Cre-Transgenic Mice , 2011, Frontiers in Systems Neuroscience.

[151]  Lief E. Fenno,et al.  Principles for applying optogenetic tools derived from direct comparative analysis of microbial opsins , 2011, Nature Methods.

[152]  Mathew Tantama,et al.  Optogenetic reporters: Fluorescent protein-based genetically encoded indicators of signaling and metabolism in the brain. , 2012, Progress in brain research.

[153]  K. Deisseroth,et al.  Optogenetic stimulation of a hippocampal engram activates fear memory recall , 2012, Nature.

[154]  Hanchuan Peng,et al.  mGRASP enables mapping mammalian synaptic connectivity with light microscopy , 2011, Nature Methods.

[155]  David C Rowland,et al.  Generation of a Synthetic Memory Trace , 2012, Science.

[156]  Michael Q. Zhang,et al.  SNARE Protein Recycling by αSNAP and βSNAP Supports Synaptic Vesicle Priming , 2012, Neuron.

[157]  Jochen F Staiger,et al.  Unique functional properties of somatostatin-expressing GABAergic neurons in mouse barrel cortex , 2012, Nature Neuroscience.

[158]  Silvia Arber,et al.  Motor Circuits in Action: Specification, Connectivity, and Function , 2012, Neuron.

[159]  Mark H. Ellisman,et al.  Engineered ascorbate peroxidase as a genetically-encoded reporter for electron microscopy , 2012, Nature Biotechnology.

[160]  Hongkui Zeng,et al.  A Cre-Dependent GCaMP3 Reporter Mouse for Neuronal Imaging In Vivo , 2012, The Journal of Neuroscience.

[161]  Jasper Akerboom,et al.  Optimization of a GCaMP Calcium Indicator for Neural Activity Imaging , 2012, The Journal of Neuroscience.

[162]  Hongkui Zeng,et al.  Mouse transgenic approaches in optogenetics. , 2012, Progress in brain research.

[163]  R. Tsien,et al.  pHTomato: A genetically-encoded indicator that enables multiplex interrogation of synaptic activity , 2012, Nature Neuroscience.

[164]  Frances S. Chance,et al.  Erratum: Orthogonal micro-organization of orientation and spatial frequency in primate primary visual cortex , 2013, Nature Neuroscience.

[165]  Vincent A. Pieribone,et al.  Single Action Potentials and Subthreshold Electrical Events Imaged in Neurons with a Fluorescent Protein Voltage Probe , 2012, Neuron.

[166]  Chandra L Tucker,et al.  Manipulating cellular processes using optical control of protein-protein interactions. , 2012, Progress in brain research.

[167]  Benjamin F. Grewe,et al.  Two-photon optogenetic toolbox for fast inhibition, excitation and bistable modulation , 2012, Nature Methods.

[168]  Raymond K. Auerbach,et al.  An Integrated Encyclopedia of DNA Elements in the Human Genome , 2012, Nature.

[169]  Y. Dan,et al.  Clonally Related Visual Cortical Neurons Show Similar Stimulus Feature Selectivity , 2012, Nature.

[170]  Kenji F. Tanaka,et al.  Expanding the repertoire of optogenetically targeted cells with an enhanced gene expression system. , 2012, Cell reports.

[171]  Claudio Mussolino,et al.  TALE nucleases: tailored genome engineering made easy. , 2012, Current opinion in biotechnology.

[172]  Walther Akemann,et al.  Imaging neural circuit dynamics with a voltage-sensitive fluorescent protein. , 2012, Journal of neurophysiology.

[173]  Rafael Yuste,et al.  Two-photon optogenetics of dendritic spines and neural circuits in 3D , 2012, Nature Methods.

[174]  Lin Tian,et al.  Neural activity imaging with genetically encoded calcium indicators. , 2012, Progress in brain research.

[175]  Lee E. Edsall,et al.  A map of the cis-regulatory sequences in the mouse genome , 2012, Nature.

[176]  Fan Wang,et al.  Intersectional Cre Driver Lines Generated Using Split-Intein Mediated Split-Cre Reconstitution , 2012, Scientific Reports.

[177]  Yuji Ikegaya,et al.  An Improved Genetically Encoded Red Fluorescent Ca2+ Indicator for Detecting Optically Evoked Action Potentials , 2012, PloS one.

[178]  C. Lois,et al.  Genetic Labeling of Neuronal Subsets through Enhancer Trapping in Mice , 2012, PloS one.

[179]  Allan R. Jones,et al.  A toolbox of Cre-dependent optogenetic transgenic mice for light-induced activation and silencing , 2012, Nature Neuroscience.

[180]  D. Maclaurin,et al.  Optical recording of action potentials in mammalian neurons using a microbial rhodopsin , 2011, Nature Methods.

[181]  E. Boyden,et al.  Genetically encoded molecular tools for light-driven silencing of targeted neurons. , 2012, Progress in brain research.

[182]  Hongkui Zeng,et al.  Adeno‐Associated Viral Vectors for Anterograde Axonal Tracing with Fluorescent Proteins in Nontransgenic and Cre Driver Mice , 2012, Current protocols in neuroscience.

[183]  J. Dekker,et al.  The long-range interaction landscape of gene promoters , 2012, Nature.

[184]  H. Seung,et al.  Serial two-photon tomography: an automated method for ex-vivo mouse brain imaging , 2011, Nature Methods.

[185]  H. Taniguchi,et al.  The Spatial and Temporal Origin of Chandelier Cells in Mouse Neocortex , 2013, Science.

[186]  Le Cong,et al.  Multiplex Genome Engineering Using CRISPR/Cas Systems , 2013, Science.

[187]  James E. DiCarlo,et al.  RNA-Guided Human Genome Engineering via Cas9 , 2013, Science.

[188]  Mark T. Harnett,et al.  An optimized fluorescent probe for visualizing glutamate neurotransmission , 2013, Nature Methods.