The hormonal response to stress culminates in an increase in glucocorticoid concentration in the blood. These steroid hormones feedback to curtail the response to stress through direct actions on the brain. It has been shown that glucocorticoid actions on the brain contribute to a ‘stress refractory period’. This likely occurs through actions at stress command neurons in the paraventricular nucleus of the hypothalamus, but the mechanisms that might silence either the drive to these cells or their output is not known.
We have now shown that glucocrticoids act directly on CRH neurons to facilitate the release of endogenous opioids. These opioids act as retrograde signaling molecules and silence incoming synapses. Effectively, they function as ‘circuit breakers’ to isolate the CRH neurons from synaptic inputs and thus may promote refractoriness to subsequent stressors. This study was headed by Jaclyn Wamsteeker, a senior Ph.D. student in the lab and was published in Nature Neuroscience.