RT Journal Article SR Electronic T1 Selective activation of cholecystokinin-expressing γ-aminobutyric acid (CCK-GABA) neurons enhances memory and cognition JF eneuro JO eNeuro FD Society for Neuroscience SP ENEURO.0360-18.2019 DO 10.1523/ENEURO.0360-18.2019 A1 Paul D. Whissell A1 Jee Yoon Bang A1 Ikram Khan A1 Yu Feng Xie A1 Gustavo Parfitt A1 Martine Grenon A1 Nicholas W. Plummer A1 Patricia Jensen A1 Robert P. Bonin A1 Jun Chul Kim YR 2019 UL http://www.eneuro.org/content/early/2019/02/06/ENEURO.0360-18.2019.abstract AB 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 behavioural 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 CNO-mediated activation of CCK-GABA neurons did not alter open field or tail suspension performance and only slightly increased anxiety in the elevated plus maze. Though 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.Significance Statement CCK-GABA neurons are thought to play an important role in pathologies such as schizophrenia, but their contributions to behavior in the healthy states are poorly understood. Here we report a novel method for selectively targeting CCK-GABA neurons and manipulating their activity during behavioural tasks. Our data demonstrate that activating CCK-GABA neurons subtly affects emotional behavior but surprisingly enhances multiple memory and cognitive processes.