Neurotransmitter switching in the adult mammalian brain occurs following photoperiod-induced stress, but the mechanism of regulation is unknown. Here, Meng and colleagues demonstrate that elevated activity of dopaminergic neurons in the paraventricular nucleus of the rodent hypothalamus is required for the loss of dopamine expression after long-day photoperiod exposure. The transmitter switch occurs exclusively in paraventricular nucleus dopaminergic neurons that coexpress vesicular glutamate transporter 2; it is also accompanied by a loss of dopamine D2 receptors on corticotrophin-releasing factor (CRF) neurons, and can lead to increased release of CRF.

The authors note that activity-dependent revision of signaling provides another dimension of flexibility to regulate normal behavior. Changes in transmitter identity are also likely to contribute to various brain disorders, provoking interest in transmitter switching as a therapeutic tool for patients.

Meng D, Li HQ, Deisseroth K, Leutgeb S, Spitzer NC: Neuronal activity regulates neurotransmitter switching in the adult brain following light-induced stress. Proc. Natl. Acad. Sci. USA 115(20):5064-5071 (2018).

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