Activation of preoptic arginine vasopressin neurons induces hyperthermia in male mice.

Arginine vasopressin (AVP) is a neuropeptide acting as a neuromodulator in the brain and plays multiple roles, including a thermoregulatory one. However, the cellular mechanisms of action are not fully understood. We have carried out patch clamp recordings and calcium imaging combined with pharmacological tools and single cell RT/PCR to dissect the signaling mechanisms activated by AVP. Optogenetics combined with patch-clamp recordings was employed to determine the neurochemical nature of these neurons. We have also utilized telemetry combined with chemogenetics to study the effect of activation of AVP neurons in thermoregulatory mechanisms. Here we report that AVP neurons in the medial preoptic area (MPO) release GABA and display thermosensitive firing activity. Their optogenetic stimulation results in a decrease of the firing rates of MPO PACAP neurons. Local application of AVP potently modulates the synaptic inputs of PACAP neurons, by activating neuronal AVPr1a receptors and astrocytic AVPr1b receptors. Chemogenetic activation of MPO AVP neurons induces hyperthermia. Chemogenetic activation of all AVP neurons in the brain similarly induces hyperthermia and, in addition, decreases the endotoxin activated fever as well as the stress-induced hyperthermia.