Lateral hypothalamic melanin concentrating hormone-expressing neurons both promote and are required for cue-potentiated feeding.

Food-related stimuli can promote feeding behaviors independent of metabolic need. Cue-potentiated feeding (CPF) studies in rodents offer the potential to reveal the psychobiological mechanisms underlying learned overeating behaviors. We examined whether lateral hypothalamic area (LHA) cells expressing the feeding signal Melanin Concentrating Hormone (MCH) are sufficient and necessary for CPF. Tg(Pmch-Cre) mice received bilateral infusion of the Cre-dependent inhibitory DREADD (hM4Di), or optrode placement together with the excitatory opsin ChR2. Mice received food deprivation by restricting access to two daily meal pellets. Once weight reached ~90% from baseline, Pavlovian training commenced, in which a tone or noise conditioned stimulus (CS+) predicted the delivery of a sucrose solution, whereas a second CS- was unpaired with sucrose delivery. Following a minimum of 2 days of ad-libitum pellet access, mice underwent CPF testing, where the amount of licking for sucrose in the presence of the CS+ and CS- cues was assessed. In both the chemogenetic and optogenetic studies, control mice displayed CPF as evidenced by increased lick rate during the CS+ compared to the CS-. hM4Di-mediated inhibition of LHA MCH cells significantly impaired CPF through disrupting the capacity for the CS+ to increase the mean size of licking bursts, a measure thought to index the orosensory taste properties of sucrose. By contrast, optogenetic stimulation of LHA MCH cells enhanced CPF relative to eYFP-treated controls. Our findings support a critical role for MCH-expressing neurons in the LHA in learned overeating behavior.