Ventral hippocampal cholecystokinin interneurons gate contextual reward memory

Summary

Associating contexts with rewards depends on hippocampal circuits, with local inhibitory interneurons positioned to play an important role in shaping activity. Here, we demonstrate that the encoding of context-reward memory requires a ventral hippocampus (vHPC) to nucleus accumbens (NAc) circuit that is gated by cholecystokinin (CCK) interneurons. In a sucrose conditioned place preference (CPP) task, optogenetically inhibiting vHPC-NAc terminals impaired the acquisition of place preference. Transsynaptic rabies tracing revealed vHPC-NAc neurons were monosynaptically innervated by CCK interneurons. Using intersectional genetic targeting of CCK interneurons, ex vivo optogenetic activation of CCK interneurons increased GABAergic transmission onto vHPC-NAc neurons, while in vivo optogenetic inhibition of CCK interneurons increased cFos in these projection neurons. Notably, CCK interneuron inhibition during sucrose CPP learning increased time spent in the sucrose-associated location, suggesting enhanced place-reward memory. Our findings reveal a previously unknown hippocampal microcircuit crucial for modulating the strength of contextual reward learning.

Graphical abstract

Highlights

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  The vHPC-NAc circuit encodes contexts associated with food reward

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  vHPC cholecystokinin (CCK) interneurons inhibit vCA1→NAc projecting pyramidal cells

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  Silencing CCK interneurons in a reward context increased activity of vCA1→NAc cells

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  Silencing CCK interneurons improved the encoding of contextual reward memory

Abstract

Biological sciences; Neuroscience; Behavioral neuroscience; Cellular neuroscience