Evidence for regional heterogeneity in corticotropin-releasing factor interactions in the dorsal raphe nucleus

J Comp Neurol. 2001 Jul 9;435(4):450-63. doi: 10.1002/cne.1043.


The dorsal raphe nucleus (DR) is innervated by fibers containing the stress-related neurohormone corticotropin-releasing factor (CRF), which alters DR neuronal activity and serotonin release in rats. This study examined the relative distribution of CRF-immunoreactive fibers in the rat DR by using light level densitometry. Additionally, CRF-immunoreactive processes within specific subregions of the DR were examined at the ultrastructural level by using electron microscopy. CRF-immunoreactive fibers were organized within the DR along a caudal-rostral gradient, such that proceeding rostrally, innervation shifted from dorsolateral to ventromedial. Numerous CRF-immunoreactive axon terminals containing dense-core vesicles were found in both the caudal dorsolateral region and the rostral ventromedial/interfascicular region. These formed synaptic specializations with unlabeled dendrites and frequently contacted nonlabeled axon terminals. Semiquantitative analysis revealed certain differences between the two regions with respect to the types of associations made by CRF-immunoreactive terminals. Associations with dendrites were more frequent in the dorsolateral vs. ventromedial region (65% of 171 terminals vs. 39% of 233 terminals, respectively), whereas associations with axon terminals were more frequent in the ventromedial/interfascicular vs. the dorsolateral region (72% of 233 terminals vs. 57% of 171 terminals, respectively). Additionally, synaptic specializations between CRF-immunoreactive terminals and dendrites were more frequently asymmetric in the dorsolateral region (60%) and symmetric (49%) in the ventromedial/interfascicular region. Regional differences in CRF terminal interactions in the DR could account for the reported heterogeneous effects of CRF on DR neuronal activity and forebrain serotonin release. Importantly, the present results provide anatomical substrates for regulation of the DR by endogenous CRF.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Differentiation
  • Corticotropin-Releasing Hormone / metabolism*
  • Dendrites / metabolism
  • Dendrites / ultrastructure
  • Densitometry
  • Immunohistochemistry
  • Male
  • Microscopy, Electron
  • Nerve Fibers / metabolism
  • Nerve Fibers / ultrastructure
  • Raphe Nuclei / anatomy & histology
  • Raphe Nuclei / cytology
  • Raphe Nuclei / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Serotonin / metabolism
  • Receptors, Serotonin / ultrastructure


  • Receptors, Serotonin
  • Corticotropin-Releasing Hormone