Hippocampal cholecystokinin-expressing interneurons regulate temporal coding and contextual learning

Dámaris K Rangel Guerrero; Kira Balueva; Uladzislau Barayeu; Peter Baracskay; Igor Gridchyn; Michele Nardin; Chiara Nina Roth; Peer Wulff; Jozsef Csicsvari

doi:10.1016/j.neuron.2024.03.019

Hippocampal cholecystokinin-expressing interneurons regulate temporal coding and contextual learning

Neuron. 2024 Apr 10:S0896-6273(24)00197-1. doi: 10.1016/j.neuron.2024.03.019. Online ahead of print.

Authors

Dámaris K Rangel Guerrero¹, Kira Balueva², Uladzislau Barayeu³, Peter Baracskay³, Igor Gridchyn³, Michele Nardin³, Chiara Nina Roth³, Peer Wulff⁴, Jozsef Csicsvari⁵

Affiliations

¹ Information and Systems Sciences, Institute of Science and Technology Austria, 3400 Klosterneuburg, Austria. Electronic address: dama.ketino@gmail.com.
² Institute of Physiology, Christian-Albrechts-University Kiel, 24118 Kiel, Germany.
³ Information and Systems Sciences, Institute of Science and Technology Austria, 3400 Klosterneuburg, Austria.
⁴ Institute of Physiology, Christian-Albrechts-University Kiel, 24118 Kiel, Germany. Electronic address: p.wulff@physiologie.uni-kiel.de.
⁵ Information and Systems Sciences, Institute of Science and Technology Austria, 3400 Klosterneuburg, Austria. Electronic address: jozsef.csicsvari@ist.ac.at.

PMID: 38636524
DOI: 10.1016/j.neuron.2024.03.019

Abstract

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.

Keywords: CA1 CCK interneuron; GABAergic modulation; chemogenetics; memory; optogenetics; oscillations; place cell coding; sharp-wave ripple; theta phase precession; trajectory replay.