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Cell. 2016 Dec 1;167(6):1650-1662.e15. doi: 10.1016/j.cell.2016.11.021.

Cell-Type-Specific Optical Recording of Membrane Voltage Dynamics in Freely Moving Mice.

Author information

1
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.
2
CNC Program, Stanford University, Stanford, CA 94305, USA.
3
CNC Program, Stanford University, Stanford, CA 94305, USA; Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.
4
Departments of Bioengineering and Pediatrics, Stanford University, Stanford, CA 94305, USA.
5
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.

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.

KEYWORDS:

animal behavior; cortex; electrophysiology; field potentials; fluorescence; genetically encoded; mice; neurophysiology; optical methods; striatum; voltage sensors

PMID:
27912066
PMCID:
PMC5382987
DOI:
10.1016/j.cell.2016.11.021
[Indexed for MEDLINE]
Free PMC Article

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