Regulation of corticotropin‐releasing hormone neuronal network activity by noradrenergic stress signals

ABSTRACT: Noradrenaline is a neurotransmitter released in response to homeostatic challenge and activates the hypothalamic–pituitary–adrenal axis via stimulation of corticotropin‐releasing hormone (CRH) neurons. Here we investigated the mechanism through which noradrenaline regulates activity within the CRH neuronal network. Using a combination of in vitro GCaMP6f Ca(2+) imaging and electrophysiology, we show that noradrenaline induces a robust increase in excitability in a proportion of CRH neurons with many neurons displaying a bursting mode of activity. Noradrenaline‐induced activation required α(1)‐adrenoceptors and L‐type voltage‐gated Ca(2+) channels, but not GABA/glutamate synaptic transmission or sodium action potentials. Exposure of mice to elevated corticosterone levels was able to suppress noradrenaline‐induced activation. These results provide further insight into the mechanisms by which noradrenaline regulates CRH neural network activity and hence stress responses. [Image: see text] KEY POINTS: GCaMP6f Ca(2+) imaging and on‐cell patch‐clamp recordings reveal that corticotropin‐releasing hormone neurons are activated by noradrenaline with many neurons displaying a bursting mode of activity. Noradrenaline‐induced activation requires α(1)‐adrenoceptors. Noradrenaline‐induced Ca(2+) elevations persist after blocking GABA(A), AMPA, NMDA receptors and voltage‐gated Na(+) channels. Noradrenaline‐induced Ca(2+) elevations require L‐type voltage‐gated Ca(2+) channels. Corticosterone suppresses noradrenaline‐induced excitation.