Genetic Identification of Dopamine Neurons Required for Circadian Food Anticipatory Activity in Mice

Villa, A.; Trzeciak, J.; Wolfe, D.; Ehichioya, D.; Falkenstein, J.; Wong, J. T.; Dimalanta, L.; Kaiban, W.; Dhanoa, J.; Stevens, G.; Garcia, F.; Scarpa, L.; Chalfoun, C.; Zweifel, L.; Awatramani, R.; Palmiter, R.; Darvas, M.; Yamazaki, S.; Steele, A.

doi:10.64898/2026.03.27.714759

bioRxiv · 10.64898/2026.03.27.714759

Genetic Identification of Dopamine Neurons Required for Circadian Food Anticipatory Activity in Mice

Villa, A.·Trzeciak, J.·Wolfe, D.·Ehichioya, D.·Falkenstein, J.·Wong, J. T.·Dimalanta, L.·Kaiban, W.·Dhanoa, J.·Stevens, G.·Garcia, F.·Scarpa, L.·Chalfoun, C.·Zweifel, L.·Awatramani, R.·Palmiter, R.·Darvas, M.·Yamazaki, S.·Steele, A.

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Abstract

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 restoration of Th in substantia nigra dopamine neurons rescued anticipatory locomotion. Surprisingly, 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 profound FAA deficit. Notably, these mice exhibited a profound 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.

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Villa, A., Trzeciak, J., Wolfe, D., Ehichioya, D., Falkenstein, J., Wong, J. T., Dimalanta, L., Kaiban, W., Dhanoa, J., Stevens, G., Garcia, F., Scarpa, L., Chalfoun, C., Zweifel, L., Awatramani, R., Palmiter, R., Darvas, M., Yamazaki, S., Steele, A.. 2026-03-31. Genetic Identification of Dopamine Neurons Required for Circadian Food Anticipatory Activity in Mice. https://doi.org/10.64898/2026.03.27.714759

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