Hippocampal cholecystokinin-expressing interneurons regulate temporal coding and contextual learning

Cholecystokinin-expressing interneurons (CCKIs) are hypothesized to shape pyramidal cell-firing patterns and regulate network oscillations and related network state transitions. To directly probe their role in the CA1 region, we silenced their activity using optogenetic and chemogenetic tools in mice. Opto-tagged CCKIs revealed a heterogeneous population, and their optogenetic silencing triggered wide disinhibitory network changes affecting both pyramidal cells and other interneurons. CCKI silencing enhanced pyramidal cell burst firing and altered the temporal coding of place cells: theta phase precession was disrupted, whereas sequence reactivation was enhanced. Chemogenetic CCKI silencing did not alter the acquisition of spatial reference memories on the Morris water maze but enhanced the recall of contextual fear memories and enabled selective recall when similar environments were tested. This work suggests the key involvement of CCKIs in the control of place-cell temporal coding and the formation of contextual memories.