Decoding Neurotransmitter Switching: The Road Forward.

Neurotransmitter switching is a form of brain plasticity in which an environmental stimulus causes neurons to replace one neurotransmitter with another, often resulting in changes in behavior. This raises the possibility of applying a specific environmental stimulus to induce a switch that can enhance a desirable behavior or ameliorate symptoms of a specific pathology. For example, a stimulus inducing an increase in the number of neurons expressing dopamine could treat Parkinson's disease, or one affecting the number expressing serotonin could alleviate depression. This may already be producing successful treatment outcomes without our knowing that transmitter switching is involved, with improvement of motor function through physical activity and cure of seasonal depression with phototherapy. This review presents prospects for future investigation of neurotransmitter switching, considering opportunities and challenges for future research and describing how the investigation of transmitter switching is likely to evolve with new tools, thus reshaping our understanding of both normal brain function and mental illness.

Neuronal activity regulates neurotransmitter switching in the adult brain following light-induced stress.

Neurotransmitter switching in the adult mammalian brain occurs following photoperiod-induced stress, but the mechanism of regulation is unknown. Here, we demonstrate that elevated activity of dopaminergic neurons in the paraventricular nucleus of the hypothalamus (PaVN) in the adult rat is required for the loss of dopamine expression after long-day photoperiod exposure. The transmitter switch occurs exclusively in PaVN dopaminergic neurons that coexpress vesicular glutamate transporter 2 (VGLUT2), is accompanied by a loss of dopamine type 2 receptors (D2Rs) on corticotrophin-releasing factor (CRF) neurons, and can lead to increased release of CRF. Suppressing activity of all PaVN glutamatergic neurons decreases the number of inhibitory PaVN dopaminergic neurons, indicating homeostatic regulation of transmitter expression in the PaVN.