CRFR2 in paraventricular thalamus (PVT) mediates heat-induced anxiety in male mice

As global warming escalates, heat stress in both animals and humans has emerged as a pressing concern. As a physiological response to uncomfortable high ambient temperature, heat stress also significantly affects the emotional states of animals. The paraventricular thalamus (PVT), a pivotal brain region for stress response and emotion regulation, expresses many CRF receptors. However, the role of CRF receptors in the PVT in emotion regulation under heat conditions remains unclear. In our study, we revealed distinct sex-specific responses to heat conditions in mice: male mice presented significantly increased anxiety-like behavior, whereas female mice presented no significant alterations. After heat exposure, the male mice presented anxiety-like behavior, accompanied by a trend toward upregulation CRFR2 expression in the PVT and inhibition of the AKT/CREB signaling pathway. Conversely, reducing CRFR2 expression or inhibiting CRFR2 in the PVT effectively alleviated heat-induced anxiety-like behavior in the OFT. Furthermore, our findings revealed that chemogenetic activation of Vglut2 neurons in the PVT induced anxiety-like behavior primarily reflected in the OFT, whereas chemogenetic inhibition of these neurons mitigated heat-triggered anxiety in the OFT. Notably, the reduction in CRFR2 expression or the specific inhibition of CRFR2 in PVT Vglut2 neurons diminished heat-induced anxiety-like behavior in the OFT. Thus, our findings demonstrate that the CRFR2 and activity of Vglut2 neurons within the PVT contribute to the development of anxiety-like behavior in the OFT following heat exposure in male mice.