SLST Lab Discovers New Stress Coping Mechanism

Promulgator:SLSTRelease time:2019-03-08 Views:95

A team of scientists led by SLST Professor Dr. Hu Ji has discovered a new mechanism of stress coping. The findings, published in Current Biology, suggests reward inhibits paraventricular CRH neuronsto relieve stress. We encounter stressful stimuli every day.  Chronic, long-term stress can lead to various pathologies, including cardiovascular disease, inflammation, metabolic dysfunctions, and most prominently neurodegenerative and psychiatric disorders. Therefore, it is important for the brain to develop stress coping capabilities to promote adaptive behaviours and positive health outcomes. Chronic, uncontrollable stress can lead to various pathologies. Adaptive behaviors, such as reward consumption, control excessive stress responses and promote positive health outcomes. Corticotrophin-releasing hormone (CRH) neurons in paraventricular nucleus (PVN) represent a key hypothalamic neural population organizing endocrine, autonomic, and behavioral responses to stress by initiating hormonal cascades along the hypothalamic-pituitary-adrenal (HPA) axis and orchestrating stress-related behaviors through direct projections to limbic and autonomic brain centers. 

Using fiber photometry of Ca2+ signals within genetically identified PVN CRH neurons in freely behaving mice, Dr. Hu Ji’s team found that PVN CRH neurons are quickly and strongly inhibited by reward consumption. Reward decreases anxiety-like behavior and stress hormone surges induced by direct acute activation of PVN CRH neurons or repeated stress challenge. Repeated stress upregulates glutamatergic transmission and induces an N-methyl-D-aspartate receptor (NMDAR)-dependent burst firing pattern in these neurons, whereas reward consumption rebalances the synaptic homeostasis and abolishes the burst firing. Anatomically, PVN CRH neurons integrate widespread information from the stress- and reward-related brain areas in the forebrain and midbrain, including multiple direct long-range GABAergic afferents. Together, these findings reveal a hypothalamic circuit that organizes adaptive stress response by complementarily integrating reward and stress signals and suggest that intervening in this circuit could provide novel methods to treat stress-related disorders. 

Drs. Hu Ji and Sun Wenzhi are the corresponding author of this study. This work was supported by grants from the National Natural Science Foundation of China, Startup from ShanghaiTech and Shanghai Pujiang Talent Award.

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Fiber photometry results demonstrated that PVN CRH neurons were strongly inhibited by reward consumption.