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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 IV,
  • Jose A. Morón

摘要

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.