Fig. 2: Chemogenetic silencing of GABAergic DMHVGAT neurons induces hypothermia.

A Cartoon illustrating chemogenetic DMHVGAT neuron silencing as a strategy for inducing hypothermia. B An AAV vector with double-floxed inverted open-reading frame (DIO) hM4D(Gi) was bilaterally injected into the DMH of Vgat-cre mice, resulting in selective expression of the DREADD hM4D(Gi) in GABAergic DMHVGAT neurons. Representative photomicrograph showing DMHVGAT:hM4D expression. Scale bar: 500 μm. C Core body temperature measurements of DMHVGAT:hM4D and DMHVGAT:GFP mice (n = 9 each) after intraperitoneal (i.p.) clozapine (CLZ) delivery at t = 0 (left panel). Maximum body temperature changes were observed at t = 90 min. D Infrared thermography demonstrating decreased body temperature and tail vasoconstriction upon DMHVGAT neuron inhibition. Open field tests revealed that E average speed, F time mobile, and G total distance covered decreased upon CLZ injection in DMHVGAT:hM4D compared to DMHVGAT:GFP mice (n = 9 each). H Cumulative heatmaps depicting time spent in different locations of the open field chamber during DMHVGAT silencing. Note that DMHVGAT silencing decreased overall animal motor activity. Data are mean ± SEM values. *p < 0.05, **p < 0.01, ***p < 0.001.