Fig. 2: PVN^CRH-VMH^SF-1 projection regulates stress-induced hyperglycemia.

a Paradigm of chemogenetic activation of PVN^CRH neurons. b, c Representative image (b) and quantification (c) of c-Fos positive cell numbers in the VMH of Control and hM3Dq expression mice. n = 4 mice per group. *p = 0.01. d Paradigm of fiber-photometry recording of VMH^SF-1 neurons during footshock stress. e Approximately 30% Ca²⁺ signal change was observed in SF-1 neurons in response to footshock stimulation. n = 6 mice. f, g Paradigm of (f) anterograde tracing virus injection and typical image (g) of mGFP expression in the VMH originating from CRH afferents. h Paradigm of photo-stimulation of PVN → VMH in Crh-Cre mice. i Example traces for light-evoked time-locked EPSC in the VMH neurons. j, k Paradigm of pseudorabies virus mediated retrograde tracing (j) and representative image (k). l Approximately, 42% SF-1 projecting cell are CRH positive, while approximately 22% CRH neurons are projecting SF-1, n = 4 mice. m Paradigm of photo-stimulation of PVN^CRH → VMH. n Glucose level is significantly increased after exposure to blue light in ChR2 group (n = 6) compared to control group (n = 7). *p = 0.015. o Schematic of photo-inhibition of PVN^CRH → VMH during footshock. p Inhibition of PVN^CRH → VMH suppressed stress-induced blood glucose in fast stage (**p = 0.008, control vs eNpHR, n = 6 per group). $p = 0.017, when compared to baseline in control group. q Paradigm of microinjection of CRH receptor antagonist Astressin in the VMH. r Administration of Astressin blocked glucose increases of fast glucose response (*p = 0.043, Vehicle vs Astressin, n = 7 per group). $$p = 0.004, when compared to baseline in vehicle group. Multi-time point data were analyzed by two-way repeated-measures ANOVA with LSD post hoc comparison, otherwise use two-sided t test. All data shown as means ± SEM. Source data are provided as a Source Date file.