title: Mapping Anatomy to Behavior in Thy1:18 ChR2-YFP Transgenic Mice Using Optogenetics.
abstract: Linking the activity of defined neural populations with behavior is a key goal of neuroscience. In the context of controlling behavior, electrical stimulation affords researchers precision in the temporal domain with gross regional specificity, whereas pharmacology allows for more specific manipulation of cell types, but in the absence of temporal precision. The use of microbial opsins--light activated, genetically encoded ion channels and pumps--to control mammalian neurons now allows researchers to "sensitize" genetically and/or topologically defined populations of neurons to light to induce either depolarization or hyperpolarization in both a cell-type-specific and temporally precise manner not achievable with previous techniques. Here, we describe the use of transgenic mice expressing the blue-light gated cation channel Channelrhodopsin-2 (ChR2) under control of the Thy1 promoter for the purpose of linking neuronal activity to behavior through restricted delivery of light to an anatomic region of interest. The surgical procedure for implanting a fiber-optic light delivery guide into the mouse brain, the process of optically stimulating the brain in a behaving animal, and post hoc evaluation are given, along with necessary reagents and discussion of common technical problems and their solutions.
authors.affiliation: Stanford Neuroscience and Medical Scientist Training Programs, Stanford University, Stanford, California 94305;
authors.forename: Lief E
authors.initials: LE
authors.lastname: Fenno
authors.affiliation: Gladstone Institute of Neurological Disease, University of California San Francisco, San Francisco, California 94158;
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Gunaydin
authors.affiliation: Howard Hughes Medical Institute and Stanford Bioengineering and Psychiatry, Stanford University, Stanford, California 94305.
authors.forename: Karl
authors.initials: K
authors.lastname: Deisseroth
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001522:Behavior, Animal / Q000502:physiology*; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D001931:Brain Mapping; D000075402:Channelrhodopsins; D004558:Electric Stimulation; D004567:Electrodes, Implanted; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000502:physiology; D055100:Optical Fibers; D062308:Optogenetics / Q000379:methods*; D010775:Photic Stimulation
chemical_list: D001426:Bacterial Proteins; D000075402:Channelrhodopsins; D008164:Luminescent Proteins; C054562:yellow fluorescent protein, Bacteria