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

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 r elative distribution of CRF-immunoreactive fibers in the rat DR by using li ght level densitometry. Additionally, CRFimmunoreactive processes within sp ecific subregions of the DR were examined at the ultrastructural level by u sing electron microscopy. CRF-immunoreactive fibers were organized within t he DR along a caudal-rostral gradient, such that proceeding rostrally, inne rvation shifted from dorsolateral to ventromedial. Numerous CRF-immunoreact ive axon terminals containing dense-core vesicles were found in both the ca udal dorsolateral region and the rostral ventromedial/interfascicular regio n. These formed synaptic specializations with unlabeled dendrites and frequ ently contacted nonlabeled axon terminals. Semiquantitative analysis reveal ed certain differences between the two regions with respect to the types of associations made by CRF-immunoreactive terminals. Associations with dendr ites were more frequent in the dorsolateral vs. ventromedial region (65% of 171 terminals vs. 39% of 233 terminals, respectively), whereas association s with axon terminals were more frequent in the ventromedial/interfascicula r vs, the dorsolateral region (72% of 233 terminals vs. 57% of 171 terminal s, respectively). Additionally, synaptic specializations between CRF-immuno reactive terminals and dendrites were more frequently asymmetric in the dor solateral region (60%) and symmetric (49%) in the ventromedial/interfascicu lar region. Regional differences in CRF terminal interactions in the DR cou ld account for the reported heterogeneous effects of CRF on DR neuronal act ivity and forebrain serotonin release. Importantly, the present results pro vide anatomical substrates for regulation of the DR by endogenous CRF. (C) 2001 Wiley-Liss, Inc.