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

Apr 10, 2026bioRxiv : the preprint server for biology

Genes that identify dopamine nerve cells needed for mice’s daily activity before mealtime

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Circadian Biology on OpenScience ↗PubMed ↗DOI ↗

Abstract

Broad deletion of dopamine transporter-expressing neurons nearly abolished food anticipatory activity (FAA) in mice.

Striatal dopamine signaling through D1 receptors is linked to food anticipatory activity.
Viral restoration of dopamine signaling in substantia nigra neurons can rescue anticipatory locomotion.
Deletion of several large dopamine neuron populations had minimal impact on FAA.
A specific deletion affecting 25% of substantia nigra dopamine neurons led to a significant FAA deficit.
Mice with this specific deletion maintained food-seeking behavior but lost anticipatory locomotion.
These findings indicate a genetic dissociation between the circadian prediction of food availability and the behavioral expression of that prediction.

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Anticipating daily food availability is a conserved circadian behavior that persists even in animals lacking the suprachiasmatic nucleus, yet the neural substrates of this behavior remain poorly defined. Striatal dopamine signaling through D1 receptors promotes food anticipatory activity (FAA), but the dopaminergic neurons responsible are unknown. Here, we conditionally deleted() from genetically defined dopaminergic neuronal populations in mice. Broad deletion ofin dopamine transporter-expressing neurons nearly abolished FAA, while viral restoration ofin substantia nigra neurons was sufficient to rescue anticipatory locomotion. Surprisingly, deletion offrom several large molecularly defined dopamine neuron populations had little effect on FAA. In contrast,deletion using, affecting a relatively small subset (25%) of substantia nigra dopamine neurons, produced a profound FAA deficit. Notably, these mice retained anticipatory food-seeking behavior but failed to express anticipatory locomotion. These findings identify a small Calbindin1dopamine population that is required for the motor expression, but not the timekeeping, of food anticipation, revealing a genetic dissociation between circadian prediction and behavioral output. tyrosine hydroxylase Th Th Th Th Th Calb1Cre +