A Dorsal Hippocampus-Accumbens Circuit Motif to Guide Appetitive Memory in Space

Abstract

Retrieving and acting upon memories of food-predicting environments are essential for survival. Pyramidal cells (PYRs) in dorsal CA1 hippocampus (dCA1) of the mammalian brain provide mnemonic representations of space. While dCA1 PYRs cannot directly access motor centers, the brain substrates by which these internal representations guide appetitive behavior are unknown. Here, we uncover a circuit motif embedded in the nucleus accumbens (NAc) that enables the behavioral readout of reward-place memories. By monitoring neuronal ensemble activity in mouse dCA1-NAc pathway, combined with cell-type-selective optogenetic manipulations of dCA1-input-defined postsynaptic neurons, we show that PYRs innervate and engage NAc parvalbumin-expressing fast-spiking interneurons (PV+ FSIs) to influence medium spiny neuron (MSN) firing and thus, NAc output. This motif is specialized for memory-guided appetitive behavior, being dispensable for spatial novelty detection and hedonic motivation. Our findings demonstrate that this PYR-PV+ FSI-MSN circuit motif instantiates a limbic-motor interface for hippocampal representations of space to promote behaviorally-effective appetitive memory.