Centrally Projecting Edinger-Westphal Nucleus in the Control of Sympathetic Outflow and Energy Homeostasis

The centrally projecting Edinger-Westphal nucleus (EWcp) is a midbrain neuronal group, adjacent but segregated from the preganglionic Edinger-Westphal nucleus that projects to the ciliary ganglion. The EWcp plays a crucial role in stress responses and in maintaining energy homeostasis under conditions that require an adjustment of energy expenditure, by virtue of modulating heart rate and blood pressure, thermogenesis, food intake, and fat and glucose metabolism. This modulation is ultimately mediated by changes in the sympathetic outflow to several effector organs, including the adrenal gland, heart, kidneys, brown and white adipose tissues and pancreas, in response to environmental conditions and the animal's energy state, providing for appropriate energy utilization. Classic neuroanatomical studies have shown that the EWcp receives inputs from forebrain regions involved in these functions and projects to presympathetic neuronal populations in the brainstem. Transneuronal tracing with pseudorabies virus has demonstrated that the EWcp is connected polysynaptically with central circuits that provide sympathetic innervation to all these effector organs that are critical for stress responses and energy homeostasis. We propose that EWcp integrates multimodal signals (stress, thermal, metabolic, endocrine, etc.) and modulates the sympathetic output simultaneously to multiple effector organs to maintain energy homeostasis under different conditions that require adjustments of energy demands.