Peptidergic Edinger–Westphal neurons and the energy-dependent stress response

The continuously changing environment demands for adequate stress responses to maintain the internal dynamic equilibrium of body and mind. A successful stress response requires energy, in an amount matching the severity of the stressor and the type of response (‘fight, flight or freeze’). The stress response is generated by the central nervous system, which needs to be informed about both the threatening stressor and the availability of energy. In this review, evidence is considered for a role of the midbrain Edinger–Westphal centrally projecting neuron population (EWcp; synonym: non-preganglionic Edinger–Westphal nucleus) in the energy-dependent stress adaptation response. It deals with studies on the neurochemical organization of the EWcp with particular reference to the neuropeptides urocortin-1 and cocaine- and amphetamine-regulated transcript peptide, on the EWcp responses to different types of stressor (e.g., acute and chronic) and a changed energy state (e.g., fasting and leptin change), and on the sex-specificity of these responses. Finally, a model is presented for the way the EWcp might contribute to the coordination of the energy-dependent stress adaptation response.

► This review is on the role of the midbrain Edinger–Westphal (EW) nucleus in the energy-dependent stress response.
► It first deals with EW structure and its neuropeptides like urocortin-1 and cocaine- and amphetamine-regulated transcript.
► Then, attention is to (sex-specific) EW responses to acute and chronic stressors, fasting and adipose leptin signaling.
► Finally, we propose how the EW controls adaptation by integrating information on adverse stressors and available energy.