Elucidating the role of the supramammillary nucleus in motivational processes

Authors

• AJ Kesner
• S Ikemoto

Abstract

Motivational capacity to interact with the environment is fundamental for everyday healthy living. Motivated behaviors are ultimately manifested through reward and aversion processes, where animals must approach positive ‘rewarding’ stimuli and avoid negative ‘aversive’ stimuli to survive. When the neural mechanisms mediating these basic processes go awry, individuals may suffer from motivational disorders such as addiction, obesity, anxiety, and depression. The supramammillary nucleus (SuM), is a small nucleus that provides dense projections throughout the cerebrum. Past research on SuM has focused on its role in arousal, learning, and memory. Our lab previously found that pharmacological stimulation of SuM neurons can reinforce behavior, i.e. it is rewarding. In this study, we first confirmed that excitation of SuM neurons is rewarding using a self-stimulation procedure where mice were asked to press a lever to receive optogenetic stimulation of SuM neurons. Mice with optic fibers and viral-vector mediated expression of channelrhodopsin-2 (ChR2) in SuM, but not in areas adjacent to SuM, learned to press on a lever to earn optogenetic stimulation. Next, using a Cre-dependent ChR2 vector we found the rewarding effects of stimulating SuM neurons is mediated by glutamatergic neurons, but not dopaminergic or GABAergic neurons. In particular, stimulation of glutamatergic neurons projecting to the septal area, but not other sites, is highly rewarding. Lastly, using in-vivo electrophysiology recording in awake mice we found SuM neurons respond to reward (sucrose) seeking and consumption. Our results implicate the SuM and in motivational processes and warrants future research into its role in motivationally relevant psychiatric disorders.

Scientific Focus Area: Neuroscience

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