A ventral striatal-orexin/hypocretin circuit modulates approach but not consumption of food

SummaryFeeding is at once both a basic biological need and a function set in a complex system of competing motivational drivers. Orexin/hypocretin neurons are located exclusively within the lateral hypothalamus (LH) and are commonly implicated in feeding, arousal, and motivated behavior, although largely based on studies employing long-term systemic manipulations. Here we show how orexin neurons in freely behaving mice respond in real time to food presentations, and how this response is modulated by differences in metabolic state and salience. Orexin neurons increased activity during approach to food, and this activity declined to baseline at the start of consummatory behavior. Furthermore, the activity of orexin neurons on approach was enhanced by manipulations of metabolic state, and increased food salience. We investigated the nucleus accumbens shell (NAcSh) as a candidate afferent region to inhibit LH orexin neurons following approach, and using projection and cell type-specific electrophysiology, demonstrated that the NAcSh forms both direct and indirect inhibitory projections to LH orexin cells. Together these findings reveal that the activity of orexin neurons is associated with food approach rather than consumption, is modulated by motivationally relevant factors, and that the NAcSh-LH pathway is capable of suppressing orexin cell recruitment.