Andrew P Villa, Jacqueline Trzeciak, Damien Wolfe, David E Ehichioya, Jeffrey Falkenstein, Justine T Wong, Renqi Wu, Lauren Dimalanta, Wyatt Kaiban, Jaskaran Dhanoa, Gregory Stevens, Moueez Shah, Fernando Garcia, Lori Scarpa, Chris Chalfoun, Larry S Zweifel, Rajeshwar Awatramani, Richard D Palmiter, Martin Darvas, Shin Yamazaki, Andrew D Steele
Anticipating daily food availability is a conserved circadian behavior that persists even in animals lacking the suprachiasmatic nucleus, yet its neural substrates remain poorly defined. Previous studies implicated dopamine signaling in food-anticipatory activity (FAA) but lacked the resolution to identify the responsible neuronal population. Here, we conditionally deleted tyrosine hydroxylase (Th) from molecularly defined dopamine neuron populations in mice. Broad deletion of Th in dopamine transporter-expressing neurons nearly abolished FAA, whereas the restoration of Th in substantia nigra dopamine neurons rescued anticipatory locomotion. Surprisingly, the deletion of Th from several large dopamine neuron populations had little effect on FAA. In contrast, deletion using Calb1Cre, targeting only ∼25% of substantia nigra dopamine neurons, produced a strong suppression of FAA. Notably, these mice exhibited a loss of anticipatory locomotion while retaining substantial anticipatory food-seeking behavior. These findings identify a small Calbindin1+ dopamine population required for anticipatory locomotion and demonstrate that distinct behavioral components of food anticipation can be genetically dissociated.