Chemogenetic Modulation of Preoptic Neurons Decreases Body Temperature and Heart Rate

The preoptic area of the hypothalamus is critical for regulation of brain-body interaction, including circuits that control vital signs such as body temperature and heart rate. The preoptic area contains approximately 70 molecularly distinct cell types. The gene is expressed in a subset of preoptic area cell types. It encodes the GABA receptor ε-subunit, which is thought to confer resistance to anesthetics at the molecular level, but the function of cells in the brain remains largely unknown. We generated and have extensively characterized a knock-in mouse line and used chemogenetic tools to interrogate the function of cells in the preoptic area. Comparison with macaque expression revealed the conserved character of cells in the preoptic area. In awake mice, we found that chemogenetic activation of neurons in the preoptic area reduced body temperature, whereas chemogenetic inhibition had no effect. Furthermore, chemogenetic inhibition of neurons in the preoptic area decreased the heart rate, whereas chemogenetic activation had no effect under isoflurane anesthesia. These findings suggest an important role of preoptic neurons in maintaining vital signs such as body temperature and heart rate during wakefulness and under anesthesia.