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.


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*


  • Parvalbumins
  • Cholecystokinin