Ultrafast Two-Photon Imaging of a High-Gain Voltage Indicator in Awake Behaving Mice.
Cell
; 179(7): 1590-1608.e23, 2019 12 12.
Article
in En
| MEDLINE
| ID: mdl-31835034
Optical interrogation of voltage in deep brain locations with cellular resolution would be immensely useful for understanding how neuronal circuits process information. Here, we report ASAP3, a genetically encoded voltage indicator with 51% fluorescence modulation by physiological voltages, submillisecond activation kinetics, and full responsivity under two-photon excitation. We also introduce an ultrafast local volume excitation (ULoVE) method for kilohertz-rate two-photon sampling in vivo with increased stability and sensitivity. Combining a soma-targeted ASAP3 variant and ULoVE, we show single-trial tracking of spikes and subthreshold events for minutes in deep locations, with subcellular resolution and with repeated sampling over days. In the visual cortex, we use soma-targeted ASAP3 to illustrate cell-type-dependent subthreshold modulation by locomotion. Thus, ASAP3 and ULoVE enable high-speed optical recording of electrical activity in genetically defined neurons at deep locations during awake behavior.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Theta Rhythm
/
Wakefulness
/
Brain
/
GTPase-Activating Proteins
/
Microscopy, Fluorescence, Multiphoton
/
Optogenetics
Limits:
Animals
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Female
/
Humans
/
Male
Language:
En
Journal:
Cell
Year:
2019
Type:
Article
Affiliation country:
France