Fig. 5: Optogenetic conditioning of VMPO^LepR neurons induces heat tolerance.

a, Experimental paradigm used for continuous optogenetic activation of VMPO^LepR neurons before the heat endurance assay. LepR-Cre animals were injected with Cre-dependent ChR2 AAV particles into the rostral POA and either not stimulated or stimulated for 1 or 3 d by blue light at a low frequency (1 Hz) before the heat endurance assay. All animals were optogenetically stimulated during the heat endurance assay. b, Body temperature of individual mice subjected to optogenetic conditioning. Only those animals conditioned for 3 d had acquired heat tolerance and performed robustly in the heat endurance assay. Animals that reached the cut-off temperature of 41.5 °C were removed from the assay; assay duration was limited to 9 h. c, Endurance time (t_E) of the differently conditioned groups shown in b. Box plots show the median and IQR. Kruskal–Wallis test: H = 8.649, d.f. = 2, P = 0.0019, with Dunn’s pairwise comparison test and Bonferroni’s corrections: ^**P = 0.0088 (Opto:3 d Opto) (N = 4 per group (Extended Data Fig. 8)).