Next-generation transgenic mice for optogenetic analysis of neural circuits

Here we characterize several new lines of transgenic mice useful for optogenetic analysis of brain circuit function. These mice express optogenetic probes, such as enhanced halorhodopsin or several different versions of channelrhodopsins, behind various neuron-specific promoters. These mice permit photoinhibition or photostimulation both in vitro and in vivo. Our results also reveal the important influence of fluorescent tags on optogenetic probe expression and function in transgenic mice.

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

[2]  J. Strahlendorf,et al.  Ionic contributions to the oscillatory firing activity of rat Purkinje cells in vitro , 1993, Brain Research.

[3]  Stefan R. Pulver,et al.  Genetically encoded calcium indicators for multi-color neural activity imaging and combination with optogenetics , 2013, Front. Mol. Neurosci..

[4]  T. Ishizuka,et al.  Kinetic evaluation of photosensitivity in genetically engineered neurons expressing green algae light-gated channels , 2006, Neuroscience Research.

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

[6]  R. Tsien,et al.  Improved monomeric red, orange and yellow fluorescent proteins derived from Discosoma sp. red fluorescent protein , 2004, Nature Biotechnology.

[7]  S. Arber,et al.  A Developmental Switch in the Response of DRG Neurons to ETS Transcription Factor Signaling , 2005, PLoS biology.

[8]  K. Deisseroth,et al.  Red-shifted optogenetic excitation: a tool for fast neural control derived from Volvox carteri , 2008, Nature Neuroscience.

[9]  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.

[10]  E. Bamberg,et al.  Light Activation of Channelrhodopsin-2 in Excitable Cells of Caenorhabditis elegans Triggers Rapid Behavioral Responses , 2005, Current Biology.

[11]  Stefan Wölfl,et al.  Faithful Expression of Multiple Proteins via 2A-Peptide Self-Processing: A Versatile and Reliable Method for Manipulating Brain Circuits , 2009, The Journal of Neuroscience.

[12]  K. Deisseroth,et al.  eNpHR: a Natronomonas halorhodopsin enhanced for optogenetic applications , 2008, Brain cell biology.

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

[14]  Karel Svoboda,et al.  Long-Range Neuronal Circuits Underlying the Interaction between Sensory and Motor Cortex , 2011, Neuron.

[15]  K. Deisseroth,et al.  Ultrafast optogenetic control , 2010, Nature Neuroscience.

[16]  Tobias Rose,et al.  Optimizing the spatial resolution of Channelrhodopsin-2 activation , 2008, Brain cell biology.

[17]  O. Kiehn,et al.  Activation of groups of excitatory neurons in the mammalian spinal cord or hindbrain evokes locomotion , 2010, Nature Neuroscience.

[18]  R. Gottlieb,et al.  Novel methods for measuring cardiac autophagy in vivo. , 2009, Methods in enzymology.

[19]  E. Boyden,et al.  Multiple-Color Optical Activation, Silencing, and Desynchronization of Neural Activity, with Single-Spike Temporal Resolution , 2007, PloS one.

[20]  K. Svoboda,et al.  Myosin-dependent targeting of transmembrane proteins to neuronal dendrites , 2009, Nature Neuroscience.

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

[22]  Jörg Bäurle,et al.  Dependence of parvalbumin expression on Purkinje cell input in the deep cerebellar nuclei , 1998, The Journal of comparative neurology.

[23]  Feng Zhang,et al.  Multimodal fast optical interrogation of neural circuitry , 2007, Nature.

[24]  G. Augustine,et al.  Distribution of functional glutamate and GABA receptors on hippocampal pyramidal cells and interneurons. , 2000, Journal of neurophysiology.

[25]  Bradley J. Baker,et al.  Genetically encoded fluorescent voltage sensors using the voltage-sensing domain of Nematostella and Danio phosphatases exhibit fast kinetics , 2012, Journal of Neuroscience Methods.

[26]  N. Jenkins,et al.  Highly restricted expression of Cre recombinase in cerebellar Purkinje cells , 2004, Genesis.

[27]  Nathan R. Wilson,et al.  Division and subtraction by distinct cortical inhibitory networks in vivo , 2012, Nature.

[28]  Haruo Kasai,et al.  Spatiotemporal Dynamics of Functional Clusters of Neurons in the Mouse Motor Cortex during a Voluntary Movement , 2013, The Journal of Neuroscience.

[29]  David W Piston,et al.  Fluorescent proteins at a glance , 2011, Journal of Cell Science.

[30]  J. Livet,et al.  A technicolour approach to the connectome , 2008, Nature Reviews Neuroscience.

[31]  J. Magee.  Dendritic integration of excitatory synaptic input , 2000, Nature Reviews Neuroscience.

[32]  E. Bamberg,et al.  Ultra light-sensitive and fast neuronal activation with the Ca2+-permeable channelrhodopsin CatCh , 2011, Nature Neuroscience.

[33]  Edward S Boyden,et al.  Acute Optogenetic Silencing of Orexin/Hypocretin Neurons Induces Slow-Wave Sleep in Mice , 2011, The Journal of Neuroscience.

[34]  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.

[35]  K. Svoboda,et al.  Sparse optical microstimulation in barrel cortex drives learned behaviour in freely moving mice , 2008, Nature.

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

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

[38]  George J. Augustine,et al.  Optogenetic probing of functional brain circuitry , 2011, Experimental physiology.

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

[40]  W. C. Hall,et al.  High-speed mapping of synaptic connectivity using photostimulation in Channelrhodopsin-2 transgenic mice , 2007, Proceedings of the National Academy of Sciences.

[41]  K. Deisseroth,et al.  Neural substrates of awakening probed with optogenetic control of hypocretin neurons , 2007, Nature.

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

[43]  H. Markram,et al.  Interneurons of the neocortical inhibitory system , 2004, Nature Reviews Neuroscience.

[44]  Dieter Jaeger,et al.  The Contribution of NMDA and AMPA Conductances to the Control of Spiking in Neurons of the Deep Cerebellar Nuclei , 2003, The Journal of Neuroscience.

[45]  Benjamin R. Arenkiel,et al.  In Vivo Light-Induced Activation of Neural Circuitry in Transgenic Mice Expressing Channelrhodopsin-2 , 2007, Neuron.

[46]  Abigail L. Person,et al.  Purkinje neuron synchrony elicits time-locked spiking in the cerebellar nuclei , 2011, Nature.

[47]  Karl Deisseroth,et al.  Functional Control of Transplantable Human ESC‐Derived Neurons Via Optogenetic Targeting , 2010, Stem cells.

[48]  Olaf Sporns,et al.  The Human Connectome: A Structural Description of the Human Brain , 2005, PLoS Comput. Biol..

[49]  K. Deisseroth,et al.  Phasic Firing in Dopaminergic Neurons Is Sufficient for Behavioral Conditioning , 2009, Science.

[50]  Upinder S Bhalla,et al.  Non-redundant odor coding by sister mitral cells revealed by light addressable glomeruli in the mouse , 2010, Nature Neuroscience.

[51]  Thomas Knöpfel,et al.  Genetically encoded optical indicators for the analysis of neuronal circuits , 2012, Nature Reviews Neuroscience.

[52]  M. Meyer,et al.  Cre recombinase expression in cerebellar Purkinje cells , 2000, Genesis.

[53]  Kenji F. Tanaka,et al.  Functional Connectome of the Striatal Medium Spiny Neuron , 2011, The Journal of Neuroscience.

[54]  Y. Kawaguchi.  Physiological subgroups of nonpyramidal cells with specific morphological characteristics in layer II/III of rat frontal cortex , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[55]  R. Llinás,et al.  Electrophysiological properties of in vitro Purkinje cell dendrites in mammalian cerebellar slices. , 1980, The Journal of physiology.

[56]  M. Davidson,et al.  Engineered fluorescent proteins: innovations and applications , 2009, Nature Methods.

[57]  F. Tempia,et al.  Postsynaptic currents in deep cerebellar nuclei. , 2001, Journal of neurophysiology.

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

[59]  S. Schiffmann,et al.  ‘New’ functions for ‘old’ proteins: The role of the calcium-binding proteins calbindin D-28k, calretinin and parvalbumin, in cerebellar physiology. Studies with knockout mice , 2002, The Cerebellum.

[60]  R. Marois,et al.  Capacity limits of information processing in the brain , 2005, Trends in Cognitive Sciences.

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

[62]  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.

[63]  K. Deisseroth,et al.  High-efficiency channelrhodopsins for fast neuronal stimulation at low light levels , 2011, Proceedings of the National Academy of Sciences.

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

[65]  Murtaza Z Mogri,et al.  Targeting and Readout Strategies for Fast Optical Neural Control In Vitro and In Vivo , 2007, The Journal of Neuroscience.

[66]  D. Oesterhelt,et al.  Structure of the light-driven chloride pump halorhodopsin at 1.8 A resolution. , 2000, Science.

[67]  P. Emson,et al.  Localization of parvalbumin mRNA in rat brain by in situ hybridization histochemistry , 2004, Experimental Brain Research.

[68]  M. Carandini,et al.  Parvalbumin-Expressing Interneurons Linearly Transform Cortical Responses to Visual Stimuli , 2012, Neuron.

[69]  Peggy Teo,et al.  Optogenetic mapping of brain circuitry , 2012, Other Conferences.

[70]  Peggy Teo,et al.  High-speed optogenetic circuit mapping , 2013, Photonics West - Biomedical Optics.

[71]  Karl Deisseroth,et al.  Activation of Specific Interneurons Improves V1 Feature Selectivity and Visual Perception , 2012, Nature.

[72]  H. Hellinga,et al.  Visualization of Synaptic Inhibition with an Optogenetic Sensor Developed by Cell-Free Protein Engineering Automation , 2013, The Journal of Neuroscience.

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

[74]  Lief E. Fenno,et al.  The Microbial Opsin Family of Optogenetic Tools , 2011, Cell.

[75]  Karl Deisseroth,et al.  Improved expression of halorhodopsin for light-induced silencing of neuronal activity , 2008, Brain cell biology.

[76]  Minmin Luo,et al.  Habenula “Cholinergic” Neurons Corelease Glutamate and Acetylcholine and Activate Postsynaptic Neurons via Distinct Transmission Modes , 2011, Neuron.

[77]  Peter Somogyi,et al.  Cell surface domain specific postsynaptic currents evoked by identified GABAergic neurones in rat hippocampus in vitro , 2000, The Journal of physiology.

[78]  George J. Augustine,et al.  Light-Emitting Channelrhodopsins for Combined Optogenetic and Chemical-Genetic Control of Neurons , 2013, PloS one.

[79]  Stephen J Smith,et al.  Circuit reconstruction tools today , 2007, Current Opinion in Neurobiology.

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

[81]  M. Davidson,et al.  Advances in fluorescent protein technology , 2011, Journal of Cell Science.

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

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