Alternating sources of perisomatic inhibition during behavior

Barna Dudok; Peter M Klein; Ernie Hwaun; Brian R Lee; Zizhen Yao; Olivia Fong; John C Bowler; Satoshi Terada; Fraser T Sparks; Gergely G Szabo; Jordan S Farrell; Jim Berg; Tanya L Daigle; Bosiljka Tasic; Jordane Dimidschstein; Gord Fishell; Attila Losonczy; Hongkui Zeng; Ivan Soltesz

doi:10.1016/j.neuron.2021.01.003

Alternating sources of perisomatic inhibition during behavior

Neuron. 2021 Mar 17;109(6):997-1012.e9. doi: 10.1016/j.neuron.2021.01.003. Epub 2021 Feb 1.

Authors

Barna Dudok¹, Peter M Klein², Ernie Hwaun², Brian R Lee³, Zizhen Yao³, Olivia Fong³, John C Bowler⁴, Satoshi Terada⁴, Fraser T Sparks⁴, Gergely G Szabo², Jordan S Farrell², Jim Berg³, Tanya L Daigle³, Bosiljka Tasic³, Jordane Dimidschstein⁵, Gord Fishell⁶, Attila Losonczy⁷, Hongkui Zeng³, Ivan Soltesz²

Affiliations

¹ Department of Neurosurgery, Stanford University, Stanford, CA 94305, USA. Electronic address: bdudok@stanford.edu.
² Department of Neurosurgery, Stanford University, Stanford, CA 94305, USA.
³ Allen Institute for Brain Science, Seattle, WA 98109, USA.
⁴ Department of Neuroscience, Columbia University, New York, NY 10027, USA.
⁵ Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
⁶ Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Medical School, Blavatnik Institute, Department of Neurobiology, Boston, MA 02115, USA.
⁷ Department of Neuroscience, Columbia University, New York, NY 10027, USA; Mortimer B. Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA.

Abstract

Interneurons expressing cholecystokinin (CCK) and parvalbumin (PV) constitute two key GABAergic controllers of hippocampal pyramidal cell output. Although the temporally precise and millisecond-scale inhibitory regulation of neuronal ensembles delivered by PV interneurons is well established, the in vivo recruitment patterns of CCK-expressing basket cell (BC) populations has remained unknown. We show in the CA1 of the mouse hippocampus that the activity of CCK BCs inversely scales with both PV and pyramidal cell activity at the behaviorally relevant timescales of seconds. Intervention experiments indicated that the inverse coupling of CCK and PV GABAergic systems arises through a mechanism involving powerful inhibitory control of CCK BCs by PV cells. The tightly coupled complementarity of two key microcircuit regulatory modules demonstrates a novel form of brain-state-specific segregation of inhibition during spontaneous behavior.

Keywords: CA1; CB1 receptor; GABA; Sncg; brain state; cholecystokinin; hippocampus; inhibition; interneuron; locomotion; parvalbumin.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
CA1 Region, Hippocampal / physiology*
Cholecystokinin / metabolism
Female
Interneurons / physiology*
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Parvalbumins / metabolism
Pyramidal Cells / physiology*
Synaptic Transmission / physiology*

Substances

Parvalbumins
Cholecystokinin

Abstract

Publication types

MeSH terms

Substances

Grants and funding