Supramammillary neurons projecting to the septum regulate dopamine and motivation for environmental interaction in mice

Author:

Kesner Andrew J.ORCID,Shin Rick,Calva Coleman B.,Don Reuben F.,Junn Sue,Potter Christian T.ORCID,Ramsey Leslie A.ORCID,Abou-Elnaga Ahmed F.,Cover Christopher G.,Wang Dong V.ORCID,Lu Hanbing,Yang Yihong,Ikemoto SatoshiORCID

Abstract

AbstractThe supramammillary region (SuM) is a posterior hypothalamic structure, known to regulate hippocampal theta oscillations and arousal. However, recent studies reported that the stimulation of SuM neurons with neuroactive chemicals, including substances of abuse, is reinforcing. We conducted experiments to elucidate how SuM neurons mediate such effects. Using optogenetics, we found that the excitation of SuM glutamatergic (GLU) neurons was reinforcing in mice; this effect was relayed by their projections to septal GLU neurons. SuM neurons were active during exploration and approach behavior and diminished activity during sucrose consumption. Consistently, inhibition of SuM neurons disrupted approach responses, but not sucrose consumption. Such functions are similar to those of mesolimbic dopamine neurons. Indeed, the stimulation of SuM-to-septum GLU neurons and septum-to-ventral tegmental area (VTA) GLU neurons activated mesolimbic dopamine neurons. We propose that the supramammillo-septo-VTA pathway regulates arousal that reinforces and energizes behavioral interaction with the environment.

Funder

U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry

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