Dorsal hippocampus to nucleus accumbens projections drive reinforcement via activation of accumbal dynorphin neurons

Khairunisa Mohamad Ibrahim, Nicolas Massaly, Hye-Jean Yoon, Rossana Sandoval, Allie J. Widman, Robert J. Heuermann, Sidney Williams, William Post, Sulan Pathiranage, Tania Lintz, Azra Zec, Ashley Park, Waylin Yu, Thomas L. Kash, Robert W. Gereau and Jose A. Morón ()
Additional contact information
Khairunisa Mohamad Ibrahim: Washington University Pain Center
Nicolas Massaly: Washington University Pain Center
Hye-Jean Yoon: Washington University Pain Center
Rossana Sandoval: Washington University Pain Center
Allie J. Widman: Washington University Pain Center
Robert J. Heuermann: Washington University Pain Center
Sidney Williams: Washington University Pain Center
William Post: Washington University Pain Center
Sulan Pathiranage: Washington University Pain Center
Tania Lintz: Washington University Pain Center
Azra Zec: Washington University Pain Center
Ashley Park: Washington University Pain Center
Waylin Yu: University of North Carolina at Chapel Hill School of Medicine
Thomas L. Kash: University of North Carolina at Chapel Hill School of Medicine
Robert W. Gereau: Washington University Pain Center
Jose A. Morón: Washington University Pain Center

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: Abstract The hippocampus is pivotal in integrating emotional processing, learning, memory, and reward-related behaviors. The dorsal hippocampus (dHPC) is particularly crucial for episodic, spatial, and associative memory, and has been shown to be necessary for context- and cue-associated reward behaviors. The nucleus accumbens (NAc), a central structure in the mesolimbic reward pathway, integrates the salience of aversive and rewarding stimuli. Despite extensive research on dHPC→NAc direct projections, their sufficiency in driving reinforcement and reward-related behavior remains to be determined. Our study establishes that activating excitatory neurons in the dHPC is sufficient to induce reinforcing behaviors through its direct projections to the dorso-medial subregion of the NAc shell (dmNAcSh). Notably, dynorphin-containing neurons specifically contribute to dHPC-driven reinforcing behavior, even though both dmNAcSh dynorphin- and enkephalin-containing neurons are activated with dHPC stimulation. Our findings unveil a pathway governing reinforcement, advancing our understanding of the hippocampal circuity’s role in reward-seeking behaviors.

Date: 2024
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DOI: 10.1038/s41467-024-44836-9

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