ObjectiveThe lateral periaqueductal gray (LPAG), which mainly contains glutamatergic neurons, plays an important role in social responses, pain, and offensive and defensive behaviors. Currently, the whole‐brain monosynaptic inputs to LPAG glutamatergic neurons are unknown. This study aims to explore the structural framework of the underlying neural mechanisms of LPAG glutamatergic neurons.MethodsThis study used retrograde tracing systems based on the rabies virus, Cre‐LoxP technology, and immunofluorescence analysis.ResultsWe found that 59 nuclei projected monosynaptic inputs to the LPAG glutamatergic neurons. In addition, seven hypothalamic nuclei, namely the lateral hypothalamic area (LH), lateral preoptic area (LPO), substantia innominata (SI), medial preoptic area, ventral pallidum, posterior hypothalamic area, and lateral globus pallidus, projected most densely to the LPAG glutamatergic neurons. Notably, we discovered through further immunofluorescence analysis that the inputs to the LPAG glutamatergic neurons were colocalized with several markers related to important neurological functions associated with physiological behaviors.ConclusionThe LPAG glutamatergic neurons received dense projections from the hypothalamus, especially nuclei such as LH, LPO, and SI. The input neurons were colocalized with several markers of physiological behaviors, which show the pivotal role of glutamatergic neurons in the physiological behaviors regulation by LPAG.

Graphical AbstractAdenosine mediates sleep, torpor and hibernation through P1 receptors. Recent reasearch has shown that P1 receptors play a vital role in the regulation of sleep-wake, torpor and hibernation-like states. In this review, we focus on the roles and neurobiological mechanisms of the CNS adenosine and P1 receptors in these three states. Among them, A1 and A2A receptors are key targets for sleep-wake regulation, A1Rs and A3Rs are very important for torpor induction, and activation of A1Rs is sufficient for hibernation-like state.

Stress in the endoplasmic reticulum (ER) may perturb proteostasis and activates the unfolded protein response (UPR). UPR activation is frequently observed in cancer cells and is believed to fuel cancer progression. Here, we report that one of the three UPR sensors, ATF6α, was associated with prostate cancer (PCa) development, while both genetic and pharmacological inhibition of ATF6α impaired the survival of castration‐resistance PCa (CRPC) cells. Transcriptomic analyses identified the molecular pathways deregulated upon ATF6α depletion, and also discovered considerable disparity in global gene expression between ATF6α knockdown and Ceapin‐A7 treatment. In addition, combined analyses of human CRPC bulk RNA‐seq and single‐cell RNA‐seq (scRNA‐seq) public datasets confirmed that CRPC tumors with higher ATF6α activity displayed higher androgen receptor (AR) activity, proliferative and neuroendocrine (NE) like phenotypes, as well as immunosuppressive features. Lastly, we identified a 14‐gene set as ATF6α NE gene signature with encouraging prognostic power. In conclusion, our results indicate that ATF6α is correlated with PCa progression and is functionally relevant to CRPC cell survival. Both specificity and efficacy of ATF6α inhibitors require further refinement and evaluation.