Innate social investigation behaviors are critical for animal survival and are regulated by both neural circuits and neuroendocrine factors. Our understandings for how neuropeptides regulate social interest, however, are incomplete at current stage. In this study, we identified the expression of secretin (SCT) in a subpopulation of excitatory neurons in basolateral amygdala (BLA). With distinct molecular and physiological features, BLASCT+ cells project to medial prefrontal cortex and were necessary and sufficient for promoting social investigation behaviors, whilst other BLA neurons were anxiogenic to antagonize social behaviors. Moreover, the exogenous application of SCT effectively promoted social interest in both healthy and autism spectrum disorder (ASD) model mice. These results collectively demonstrated one previously unrecognized group of amygdala neurons for mediating social behaviors and suggested promising strategies for social deficits.

Salt homeostasis is orchestrated by both neural circuits and peripheral endocrine factors. The colon is one of the primary sites for electrolyte absorption, while its potential role in modulating sodium intake remains unclear. Here, we revealed that a gastrointestinal hormone, secretin, is released from colon endocrine cells under body sodium deficiency and is indispensable for inducing salt appetite. As the neural substrate, circulating secretin activates specific receptors in the nucleus of the solitary tracts, which further activates the downstream paraventricular nucleus of the hypothalamus, resulting in enhanced sodium intake. These results demonstrated a previously unrecognized gut-brain pathway for the timely regulation of sodium homeostasis.

Aerobic exercise effectively ameliorates mental disorders including anxiety and depression. Current findings mainly attribute its neural mechanism to the improvement of adult neurogenesis, while leaving the possible circuitry mechanism unclear. In the current study, we identify the overexcitation of the medial prefrontal cortex (mPFC) to basolateral amygdala (BLA) pathway under chronic restraint stress (CRS), and 14-day treadmill exercise selectively reverses such abnormalities. Using chemogenetic approaches, we find that the mPFC-BLA circuit is necessary for preventing anxiety-like behaviors in CRS mice. These results collectively suggest a neural circuitry mechanism by which exercise training improves the resilience against environmental stress.