title: Cell-Type-Specific Optical Recording of Membrane Voltage Dynamics in Freely Moving Mice.
abstract: Electrophysiological field potential dynamics are of fundamental interest in basic and clinical neuroscience, but how specific cell types shape these dynamics in the live brain is poorly understood. To empower mechanistic studies, we created an optical technique, TEMPO, that records the aggregate trans-membrane voltage dynamics of genetically specified neurons in freely behaving mice. TEMPO has >10-fold greater sensitivity than prior fiber-optic techniques and attains the noise minimum set by quantum mechanical photon shot noise. After validating TEMPO's capacity to track established oscillations in the delta, theta, and gamma frequency bands, we compared the D1- and D2-dopamine-receptor-expressing striatal medium spiny neurons (MSNs), which are interspersed and electrically indistinguishable. Unexpectedly, MSN population dynamics exhibited two distinct coherent states that were commonly indiscernible in electrical recordings and involved synchronized hyperpolarizations across both MSN subtypes. Overall, TEMPO allows the deconstruction of normal and pathologic neurophysiological states into trans-membrane voltage activity patterns of specific cell types.
authors.affiliation: James H. Clark Center for Biomedical Engineering and Sciences, Stanford University, Stanford, CA 94305, USA; CNC Program, Stanford University, Stanford, CA 94305, USA; Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.
authors.forename: Jesse D
authors.initials: JD
authors.lastname: Marshall
authors.affiliation: CNC Program, Stanford University, Stanford, CA 94305, USA.
authors.forename: Jin Zhong
authors.initials: JZ
authors.lastname: Li
authors.affiliation: CNC Program, Stanford University, Stanford, CA 94305, USA; Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: CNC Program, Stanford University, Stanford, CA 94305, USA.
authors.forename: Yiyang
authors.initials: Y
authors.lastname: Gong
authors.affiliation: Departments of Bioengineering and Pediatrics, Stanford University, Stanford, CA 94305, USA.
authors.forename: François
authors.initials: F
authors.lastname: St-Pierre
authors.affiliation: Departments of Bioengineering and Pediatrics, Stanford University, Stanford, CA 94305, USA.
authors.forename: Michael Z
authors.initials: MZ
authors.lastname: Lin
authors.affiliation: James H. Clark Center for Biomedical Engineering and Sciences, Stanford University, Stanford, CA 94305, USA; CNC Program, Stanford University, Stanford, CA 94305, USA; Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA. Electronic address: mschnitz@stanford.edu.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Schnitzer
mesh_terms: D000818:Animals; D058256:Brain Waves; D005260:Female; D008297:Male; D051379:Mice / Q000502:physiology*; D008807:Mice, Inbred BALB C; D009482:Neurophysiology / Q000379:methods*; D056969:Voltage-Sensitive Dye Imaging / Q000379:methods*
keywords: animal behavior; cortex; electrophysiology; field potentials; fluorescence; genetically encoded; mice; neurophysiology; optical methods; striatum; voltage sensors