title: Hybrid voltage sensor imaging of electrical activity from neurons in hippocampal slices from transgenic mice.
abstract: Gene targeting with genetically encoded optical voltage sensors brings the methods of voltage imaging to genetically defined neurons and offers a method of studying circuit activity in these selected populations. The present study reports the targeting of genetically encoded hybrid voltage sensors (hVOS) to neurons in transgenic mice. The hVOS family of probes employs a membrane-targeted fluorescent protein, which generates voltage-dependent fluorescence changes in the presence of dipicrylamine (DPA) as the result of a voltage-dependent optical interaction between the two molecules. We generated transgenic mice with two different high-performance hVOS probes under control of a neuron-specific thy-1 promoter. Hippocampal slices from these animals present distinct spatial patterns of expression, and electrical stimulation evoked fluorescence changes as high as 3%. Glutamate receptor and Na(+) channel antagonists blocked these responses. One hVOS probe tested here harbors an axonal targeting motif (from GAP-43) and shows preferential expression in axons; this probe can thus report axonal voltage changes. Voltage imaging in transgenic mice expressing hVOS probes opens the door to the study of functional activity in genetically defined populations of neurons in intact neural circuits.
authors.affiliation: Department of Neuroscience, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Wang
authors.forename: Shane
authors.initials: S
authors.lastname: McMahon
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhang
authors.forename: Meyer B
authors.initials: MB
authors.lastname: Jackson
mesh_terms: D000818:Animals; D005453:Fluorescence; D006624:Hippocampus / Q000166:cytology; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008564:Membrane Potentials; D051379:Mice; D008822:Mice, Transgenic; D059906:Neuroimaging / Q000379:methods*; D009474:Neurons / Q000502:physiology*; D062308:Optogenetics; D010851:Picrates; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D008164:Luminescent Proteins; D010851:Picrates; D011994:Recombinant Proteins; C011454:dipicrylamine