An optogenetic toolbox designed for primates

Optogenetics is a technique for controlling subpopulations of neurons in the intact brain using light. This technique has the potential to enhance basic systems neuroscience research and to inform the mechanisms and treatment of brain injury and disease. Before launching large-scale primate studies, the method needs to be further characterized and adapted for use in the primate brain. We assessed the safety and efficiency of two viral vector systems (lentivirus and adeno-associated virus), two human promoters (human synapsin (hSyn) and human thymocyte-1 (hThy-1)) and three excitatory and inhibitory mammalian codon-optimized opsins (channelrhodopsin-2, enhanced Natronomonas pharaonis halorhodopsin and the step-function opsin), which we characterized electrophysiologically, histologically and behaviorally in rhesus monkeys (Macaca mulatta). We also introduced a new device for measuring in vivo fluorescence over time, allowing minimally invasive assessment of construct expression in the intact brain. We present a set of optogenetic tools designed for optogenetic experiments in the non-human primate brain.

[1]  W H Calvin,et al.  Fast and slow pyramidal tract neurons: an intracellular analysis of their contrasting repetitive firing properties in the cat. , 1976, Journal of neurophysiology.

[2]  Okihide Hikosaka,et al.  Effects on eye movements of a GABA agonist and antagonist injected into monkey superior colliculus , 1983, Brain Research.

[3]  C R Houser,et al.  Morphological diversity of immunocytochemically identified GABA neurons in the monkey sensory-motor cortex , 1983, Journal of neurocytology.

[4]  G. Leichnetz Afferent and efferent connections of the dorsolateral precentral gyrus (area 4, hand/arm region) in the macaque monkey, with comparisons to area 8 , 1986, The Journal of comparative neurology.

[5]  R. J. Mullen,et al.  NeuN, a neuronal specific nuclear protein in vertebrates. , 1992, Development.

[6]  R. McLendon,et al.  Immunohistochemistry of the Glial Fibrillary Acidic Protein: Basic and Applied Considerations , 1994, Brain pathology.

[7]  D. Benson,et al.  Alpha calcium/calmodulin-dependent protein kinase II selectively expressed in a subpopulation of excitatory neurons in monkey sensory- motor cortex: comparison with GAD-67 expression , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[8]  Pico Caroni,et al.  Overexpression of growth-associated proteins in the neurons of adult transgenic mice , 1997, Journal of Neuroscience Methods.

[9]  Dawn M. Taylor,et al.  Direct Cortical Control of 3D Neuroprosthetic Devices , 2002, Science.

[10]  Leah Krubitzer,et al.  Cortical connections of the second somatosensory area and the parietal ventral area in macaque monkeys , 2003, The Journal of comparative neurology.

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

[12]  P. Reier,et al.  Recombinant AAV viral vectors pseudotyped with viral capsids from serotypes 1, 2, and 5 display differential efficiency and cell tropism after delivery to different regions of the central nervous system. , 2004, Molecular therapy : the journal of the American Society of Gene Therapy.

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

[14]  O. Garaschuk,et al.  Cortical calcium waves in resting newborn mice , 2005, Nature Neuroscience.

[15]  J. Emerson,et al.  Prevalence of neutralizing antibodies against adeno-associated virus (AAV) types 2, 5, and 6 in cystic fibrosis and normal populations: Implications for gene therapy using AAV vectors. , 2006, Human gene therapy.

[16]  Feng Zhang,et al.  Channelrhodopsin-2 and optical control of excitable cells , 2006, Nature Methods.

[17]  David Eidelberg,et al.  Safety and tolerability of gene therapy with an adeno-associated virus (AAV) borne GAD gene for Parkinson's disease: an open label, phase I trial , 2007, The Lancet.

[18]  R. Normann,et al.  Thermal Impact of an Active 3-D Microelectrode Array Implanted in the Brain , 2007, IEEE Transactions on Neural Systems and Rehabilitation Engineering.

[19]  Feng Zhang,et al.  An optical neural interface: in vivo control of rodent motor cortex with integrated fiberoptic and optogenetic technology , 2007, Journal of neural engineering.

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

[21]  Seungho Wang,et al.  Role of PKA in the anti‐Thy‐1 antibody‐induced neurite outgrowth of dorsal root ganglionic neurons , 2007, Journal of cellular biochemistry.

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

[23]  K. Shenoy,et al.  Delay of movement caused by disruption of cortical preparatory activity. , 2007, Journal of neurophysiology.

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

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

[26]  Theresa A. Storm,et al.  In Vitro and In Vivo Gene Therapy Vector Evolution via Multispecies Interbreeding and Retargeting of Adeno-Associated Viruses , 2008, Journal of Virology.

[27]  A. Nieder,et al.  Complementary Contributions of Prefrontal Neuron Classes in Abstract Numerical Categorization , 2008, The Journal of Neuroscience.

[28]  Claire M. Brown,et al.  Live-cell microscopy – tips and tools , 2009, Journal of Cell Science.

[29]  K. Deisseroth,et al.  Bi-stable neural state switches , 2009, Nature Neuroscience.

[30]  B. Connors,et al.  Integrated device for optical stimulation and spatiotemporal electrical recording of neural activity in light-sensitized brain tissue , 2009, Journal of neural engineering.

[31]  W. Jagust,et al.  Safety and tolerability of putaminal AADC gene therapy for Parkinson disease , 2009, Neurology.

[32]  Murtaza Z Mogri,et al.  Optical Deconstruction of Parkinsonian Neural Circuitry , 2009, Science.

[33]  F. Fonnum,et al.  The importance of synapsin I and II for neurotransmitter levels and vesicular storage in cholinergic, glutamatergic and GABAergic nerve terminals , 2009, Neurochemistry International.

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

[35]  R. Reid,et al.  Direct Activation of Sparse, Distributed Populations of Cortical Neurons by Electrical Microstimulation , 2009, Neuron.

[36]  Jacob G. Bernstein,et al.  Millisecond-Timescale Optical Control of Neural Dynamics in the Nonhuman Primate Brain , 2009, Neuron.

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

[38]  Nikolaus R. McFarland,et al.  Comparison of transduction efficiency of recombinant AAV serotypes 1, 2, 5, and 8 in the rat nigrostriatal system , 2009, Journal of neurochemistry.

[39]  K. M. Chan,et al.  ACCELERATING AXON GROWTH TO OVERCOME LIMITATIONS IN FUNCTIONAL RECOVERY AFTER PERIPHERAL NERVE INJURY , 2009, Neurosurgery.

[40]  K. Obata,et al.  Preferential labeling of inhibitory and excitatory cortical neurons by endogenous tropism of adeno-associated virus and lentivirus vectors , 2009, Neuroscience.

[41]  Raag D. Airan,et al.  Optogenetic interrogation of neural circuits: technology for probing mammalian brain structures , 2010, Nature Protocols.

[42]  Differential transduction following basal ganglia administration of distinct pseudotyped AAV capsid serotypes in nonhuman primates. , 2010, Molecular therapy : the journal of the American Society of Gene Therapy.

[43]  C. Leborgne,et al.  Prevalence of serum IgG and neutralizing factors against adeno-associated virus (AAV) types 1, 2, 5, 6, 8, and 9 in the healthy population: implications for gene therapy using AAV vectors. , 2010, Human gene therapy.

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

[45]  Byron M. Yu,et al.  Roles of monkey premotor neuron classes in movement preparation and execution. , 2010, Journal of neurophysiology.

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

[47]  I. Bièche,et al.  Efficient intracerebral delivery of AAV5 vector encoding human ARSA in non-human primate. , 2010, Human molecular genetics.

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

[49]  Jessica A. Cardin,et al.  Targeted optogenetic stimulation and recording of neurons in vivo using cell-type-specific expression of Channelrhodopsin-2 , 2010, Nature Protocols.

[50]  Krishna V. Shenoy,et al.  Challenges and Opportunities for Next-Generation Intracortically Based Neural Prostheses , 2011, IEEE Transactions on Biomedical Engineering.

[51]  Tirin Moore,et al.  A reliable microinjectrode system for use in behaving monkeys , 2011, Journal of Neuroscience Methods.

[52]  R. K. Simpson Nature Neuroscience , 2022 .

[53]  Basic and Applied Considerations , .