Selective activation of cholecystokinin-expressing GABA (CCK-GABA) neurons enhances memory and cognition

Paul D. Whissell, Jee Yoon Bang, Ikram Khan, Yu Feng Xie, Gustavo M. Parfitt, Martine Grenon, Nicholas W. Plummer, Patricia Jensen, Robert P. Bonin, Jun Chul Kim

Research output: Contribution to journalArticlepeer-review

35 Scopus citations


Cholecystokinin-expressing GABAergic (CCK-GABA) neurons are perisomatic inhibitory cells that have been argued to regulate emotion and sculpt the network oscillations associated with cognition. However, no study has selectively manipulated CCK-GABA neuron activity during behavior in freely-moving animals. To explore the behavioral effects of activating CCK-GABA neurons on emotion and cognition, we utilized a novel intersectional genetic mouse model coupled with a chemogenetic approach. Specifically, we generated triple transgenic CCK-Cre;Dlx5/6-Flpe;RC::FL-hM3Dq (CCK-GABA/hM3Dq) mice that expressed the synthetic excitatory hM3Dq receptor in CCK-GABA neurons. Results showed that clozapine-N-oxide (CNO)-mediated activation of CCKGABA neurons did not alter open field (OF) or tail suspension (TS) performance and only slightly increased anxiety in the elevated plus maze (EPM). Although CNO treatment had only modestly affected emotional behavior, it significantly enhanced multiple cognitive and memory behaviors including social recognition, contextual fear conditioning, contextual discrimination, object recognition, and problem-solving in the puzzle box. Collectively, these findings suggest that systemic activation of CCK-GABA neurons minimally affects emotion but significantly enhances cognition and memory. Our results imply that CCK-GABA neurons are more functionally diverse than originally expected and could serve as a potential therapeutic target for the treatment of cognitive/memory disorders.

Original languageEnglish
Article numbere0360-18.2019
Issue number1
StatePublished - 1 Jan 2019
Externally publishedYes


  • Anxiety
  • Cholecystokinin
  • Cognition
  • GABA
  • Memory
  • Perisomatic


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