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

小鼠昼夜节律性食物预期活动所需多巴胺神经元的基因鉴定

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Abstract

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 tyrosine hydroxylase ( Th ) from genetically defined dopaminergic neuronal populations in mice. Broad deletion of Th in dopamine transporter-expressing neurons nearly abolished FAA, while viral restoration of Th in substantia nigra neurons was sufficient to rescue anticipatory locomotion. Surprisingly, deletion of Th from several large molecularly defined dopamine neuron populations had little effect on FAA. In contrast, Th deletion using Calb1 (Cre) , 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 Calbindin1 (+) dopamine 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.

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