Plasticity of intrinsic excitability across the estrous cycle in hypothalamic CRH neurons

Stress responses are highly plastic and vary across physiological states. The female estrous cycle is associated with a number of physiological changes including changes in stress responses, however, the mechanisms driving these changes are poorly understood. Corticotropin-releasing hormone (CRH) neurons are the primary neural population controlling the hypothalamic–pituitary–adrenal (HPA) axis and stress-evoked corticosterone secretion. Here we show that CRH neuron intrinsic excitability is regulated over the estrous cycle with a peak in proestrus and a nadir in estrus. Fast inactivating voltage-gated potassium channel (I(A)) currents showed the opposite relationship, with current density being lowest in proestrus compared to other cycle stages. Blocking I(A) currents equalized excitability across cycle stages revealing a role for I(A) in mediating plasticity in stress circuit function over the female estrous cycle.