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

背海马至伏隔核的投射通过激活伏隔核强啡肽神经元来驱动强化

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作者: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 4th, Jose A Morón

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.

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