Hypothalamic Supramammillary Glutamatergic Circuits Linking Salience to Mesolimbic Dopamine and Reinforcement

Dr. Satoshi Ikemoto is Chief of the Neurocircuitry of Motivation Section at NIDA.

The neural circuits that engage mesolimbic dopamine during reinforcement remain incompletely defined. We identify the supramammillary region (SuM) as a glutamatergic node capable of driving reinforcement and dopamine release. Rats learn to self-administer AMPA or nicotine directly into the SuM, and optogenetic activation of SuM VGluT2 neurons produces reinforcement and stimulation-locked dopamine release in the nucleus accumbens. These effects are mediated in part through projections to medial septum and lateral preoptic area that engage ventral tegmental area dopamine pathways. SuM VGluT2 neurons express nicotinic acetylcholine receptors and are activated by reinforcing doses of nicotine. Beyond reward, their activity tracks behavioral salience and is required for adaptive interaction with the environment. Together, these findings position the SuM as a circuit hub linking salient events to mesolimbic dopamine signaling and reinforcement.

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Hosted by Dr. Hitoshi Morikawa

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