Efferent and afferent connections of the dorsal and median raphe nuclei in the rat

Abstract

It is well established that the brainstem contains discrete groups of serotonin-containing neurons with extensive axonal processes that distribute throughout the neuroaxis. Serotonergic neurons have been implicated in a range of functions prominently including the modulation of various events and states of sleep. We describe the efferent and afferent projections of the dorsal raphe (DR) and the median raphe (MR) nuclei. DR fibers distribute widely throughout the forebrain to dopamine-containing nuclei of the ventral midbrain, the lateral hypothalamus, the midline thalamus, amygdala, the dorsal and ventral striatum and adjoining regions of the basal forebrain, and most of the cortex. In contrast to the DR, the MR is a midline/paramidline system of projections. Specifically, MR fibers mainly distribute to forebrain structures lying on or close to the midline including the medial mammillary and supramammillary nuclei, posterior and perifornical nuclei of hypothalamus, midline and intralaminar nuclei of thalamus, lateral habenula, medial zona incerta, diagonal band nuclei, septum and hippocampus. Overall, MR projections to the cortex are light. With few exceptions, DR and MR project to separate, non-overlapping regions of the forebrain - or, in effect, DR and MR share the serotonergic innervation of the forebrain. Although their outputs are distinct, DR and MR receive common sets of afferent projections from limbic cortices, the medial and lateral preoptic areas, lateral habenula, the perifornical, lateral and dorsomedial nuclei of hypothalamus, and several brainstem nuclei prominently including the midbrain and pontine central gray, locus coeruleus, laterodorsal tegmental nucleus and caudal raphe groups. In addition to common afferents, DR receives significant projections from bed nucleus of stria terminalis, lateral septum, diagonal band nuclei, substantia nigra and the tuberomammillary nucleus, while MR receives distinct projections from the medial septum, mammillary nuclei and the interpeduncular nucleus. There are few projections from the amygdala to either DR or MR. In effect, the DR and MR are positioned to integrate of vast array of information from the brainstem and limbic forebrain and through their extensive axonal network influence virtually all parts of the neuro. © 2008 Birkhäuser Verlag AG.