title: 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.
authors.affiliation: Laboratory of Chemical Neuroanatomy, Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, 05508-000 São Paulo, SP, Brazil.
authors.forename: Edmilson D
authors.initials: ED
authors.lastname: Dos Santos Júnior
authors.affiliation: Laboratory of Chemical Neuroanatomy, Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, 05508-000 São Paulo, SP, Brazil; Department of Anatomy, Institute of Biosciences, São Paulo State University, 18618-970 Botucatu, SP, Brazil; Federal University of Mato Grosso do Sul, Três Lagoas 79600-080, MS, Brazil.
authors.forename: André V
authors.initials: AV
authors.lastname: Da Silva
authors.affiliation: Laboratory of Chemical Neuroanatomy, Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, 05508-000 São Paulo, SP, Brazil; Department of Anatomy, Institute of Biosciences, São Paulo State University, 18618-970 Botucatu, SP, Brazil.
authors.forename: Kelly R T
authors.initials: KR
authors.lastname: Da Silva
authors.affiliation: Laboratory of Chemical Neuroanatomy, Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, 05508-000 São Paulo, SP, Brazil.
authors.forename: Carlos A S
authors.initials: CA
authors.lastname: Haemmerle
authors.affiliation: Laboratory of Chemical Neuroanatomy, Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, 05508-000 São Paulo, SP, Brazil; Center of Neuroscience and Behavior, Institute of Psychology, University of São Paulo, 05508-030 São Paulo, SP, Brazil.
authors.forename: Daniella S
authors.initials: DS
authors.lastname: Batagello
authors.affiliation: Laboratory of Chemical Neuroanatomy, Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, 05508-000 São Paulo, SP, Brazil.
authors.forename: Joelcimar M
authors.initials: JM
authors.lastname: Da Silva
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, 05508-000 São Paulo, SP, Brazil.
authors.forename: Leandro B
authors.initials: LB
authors.lastname: Lima
authors.affiliation: Laboratory of Chemical Neuroanatomy, Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, 05508-000 São Paulo, SP, Brazil.
authors.forename: Renata J
authors.initials: RJ
authors.lastname: Da Silva
authors.affiliation: Laboratory of Chemical Neuroanatomy, Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, 05508-000 São Paulo, SP, Brazil.
authors.forename: Giovanne B
authors.initials: GB
authors.lastname: Diniz
authors.affiliation: Laboratory of Chemical Neuroanatomy, Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, 05508-000 São Paulo, SP, Brazil.
authors.forename: Luciane V
authors.initials: LV
authors.lastname: Sita
authors.affiliation: Laboratory of Chemical Neuroanatomy, Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, 05508-000 São Paulo, SP, Brazil; Department of Molecular and Integrative Physiology, Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Carol F
authors.initials: CF
authors.lastname: Elias
authors.affiliation: Laboratory of Chemical Neuroanatomy, Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, 05508-000 São Paulo, SP, Brazil; Center of Neuroscience and Behavior, Institute of Psychology, University of São Paulo, 05508-030 São Paulo, SP, Brazil. Electronic address: jcbitten@icb.usp.br.
authors.forename: Jackson C
authors.initials: JC
authors.lastname: Bittencourt
mesh_terms: D000344:Afferent Pathways / Q000033:anatomy & histology / Q000502:physiology; D000818:Animals; D065839:Edinger-Westphal Nucleus / Q000033:anatomy & histology* / Q000502:physiology*; D004525:Efferent Pathways / Q000033:anatomy & histology* / Q000502:physiology*; D008297:Male; D009474:Neurons; D009476:Neurons, Efferent / Q000145:classification / Q000502:physiology; D051381:Rats; D020318:Rats, Long-Evans; D013116:Spinal Cord / Q000033:anatomy & histology / Q000502:physiology; D009626:Terminology as Topic
keywords: Corticotropin-releasing factor; Corticotropin-releasing factor receptors; Efferents; Feeding control; Stress response; Urocortin 1