The centrally projecting Edinger–Westphal nucleus—I: Efferents in the rat brain

Abstract

The oculomotor accessory nucleus, often referred to as the Edinger-Westphal nucleus [EW], was first identified in the 17th century. Although its most well known function is the control of pupil diameter, some controversy has arisen regarding the exact location of these preganglionic neurons. Currently, the EW is thought to consist of two different parts. The first part [termed the preganglionic EW-EWpg], which controls lens accommodation, choroidal blood flow and pupillary constriction, primarily consists of cholinergic cells that project to the ciliary ganglion. The second part [termed the centrally projecting EW-EWcp], which is involved in non-ocular functions such as feeding behavior, stress responses, addiction and pain, consists of peptidergic neurons that project to the brainstem, the spinal cord and prosencephalic regions. However, in the literature, we found few reports related to either ascending or descending projections from the EWcp that are compatible with its currently described functions. Therefore, the objective of the present study was to systematically investigate the ascending and descending projections of the EW in the rat brain. We injected the anterograde tracer biotinylated dextran amine into the EW or the retrograde tracer cholera toxin subunit B into multiple EW targets as controls. Additionally, we investigated the potential EW-mediated innervation of neuronal populations with known neurochemical signatures, such as melanin-concentrating hormone in the lateral hypothalamic area [LHA] and corticotropin-releasing factor in the central nucleus of the amygdala [CeM]. We observed anterogradely labeled fibers in the LHA, the reuniens thalamic nucleus, the oval part of the bed nucleus of the stria terminalis, the medial part of the central nucleus of the amygdala, and the zona incerta. We confirmed our EW-LHA and EW-CeM connections using retrograde tracers. We also observed moderate EW-mediated innervation of the paraventricular nucleus of the hypothalamus and the posterior hypothalamus. Our findings provide anatomical bases for previously unrecognized roles of the EW in the modulation of several physiologic systems.

Involvement of Centrally Projecting Edinger–Westphal Nucleus Neuropeptides in Actions of Addictive Drugs

“…In addition to the studies listed above, a set of comprehensive tracing studies investigating the ascending and descending projections of the EWcp have been performed recently in rats [91,92].…”

The Melanin-Concentrating Hormone as an Integrative Peptide Driving Motivated Behaviors

“…Of special importance to us is the role of UCN1 in feeding behavior, as UCN1 acts as a powerful anorectic peptide in nanomolar concentrations (Spina et al, 1996) and diet/fasting can regulate Ucn1 mRNA expression (Legendre et al, 2007; Xu et al, 2009). Júnior et al (2015) have shown that UCN1-ir neurons or the EWcp send projections to the LHA and these fibers are in close proximity to MCH-ir neurons, so this UCN1|EWcp-MCH|LHA circuit could represent the pathway through which UCN1 influences feeding behavior. Although the low levels of CRF receptors in MCH could be taken as an evidence against this particular pathway, it is noteworthy that these receptors are found on the LHA (Chalmers et al, 1995), so the action of UCN1 could involve the modulation of GABAergic or GLUergic interneuronal input to MCH neurons.…”

Oxytocin facilitates adaptive fear and attenuates anxiety responses in animal models and human studies—potential interaction with the corticotropin-releasing factor (CRF) system in the bed nucleus of the stria terminalis (BNST)

“…CeA might be the major source of CRF projection to the BNST dl (Pomrenze et al, 2015). Alternatively, Ucn1 fibers originating from the Edinger Westphal nucleus (Dos Santos Junior et al, 2015) might modulate OT release in the BNST dl via CRFR1 and CRFR2. Therefore, some of the behavioral effects observed after CRF or Urocortins infusions into the BNST dl , may be, at least partially, a result of changes in extracellular OT content.…”