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All-optical synaptic electrophysiology probes mechanism of ketamine-induced disinhibition.

Authors :
Fan LZ
Nehme R
Adam Y
Jung ES
Wu H
Eggan K
Arnold DB
Cohen AE
Source :
Nature methods [Nat Methods] 2018 Oct; Vol. 15 (10), pp. 823-831. Date of Electronic Publication: 2018 Oct 01.
Publication Year :
2018

Abstract

Optical assays of synaptic strength could facilitate studies of neuronal transmission and its dysregulation in disease. Here we introduce a genetic toolbox for all-optical interrogation of synaptic electrophysiology (synOptopatch) via mutually exclusive expression of a channelrhodopsin actuator and an archaerhodopsin-derived voltage indicator. Optically induced activity in the channelrhodopsin-expressing neurons generated excitatory and inhibitory postsynaptic potentials that we optically resolved in reporter-expressing neurons. We further developed a yellow spine-targeted Ca <superscript>2+</superscript> indicator to localize optogenetically triggered synaptic inputs. We demonstrated synOptopatch recordings in cultured rodent neurons and in acute rodent brain slice. In synOptopatch measurements of primary rodent cultures, acute ketamine administration suppressed disynaptic inhibitory feedbacks, mimicking the effect of this drug on network function in both rodents and humans. We localized this action of ketamine to excitatory synapses onto interneurons. These results establish an in vitro all-optical model of disynaptic disinhibition, a synaptic defect hypothesized in schizophrenia-associated psychosis.

Details

Language :
English
ISSN :
1548-7105
Volume :
15
Issue :
10
Database :
MEDLINE
Journal :
Nature methods
Publication Type :
Academic Journal
Accession number :
30275587
Full Text :
https://doi.org/10.1038/s41592-018-0142-8