Stress experience and hormone feedback tune distinct components of hypothalamic CRH neuron activity.

Stress leaves a lasting impression on an organism and reshapes future responses. However, the influence of past experience and stress hormones on the activity of neural stress circuits remains unclear. Hypothalamic corticotropin-releasing hormone (CRH) neurons orchestrate behavioral and endocrine responses to stress and are themselves highly sensitive to corticosteroid (CORT) stress hormones. Here, using in vivo optical recordings, we find that CRH neurons are rapidly activated in response to stress. CRH neuron activity robustly habituates to repeated presentations of the same, but not novel stressors. CORT feedback has little effect on CRH neuron responses to acute stress, or on habituation to repeated stressors. Rather, CORT preferentially inhibits tonic CRH neuron activity in the absence of stress stimuli. These findings reveal how stress experience and stress hormones modulate distinct components of CRH neuronal activity to mediate stress-induced adaptations.