Connections of the median and dorsal raphe nuclei in the rat: An autoradiographic and degeneration study

Abstract

Ascending and descending projections from the median and dorsal raphe nuclei of the midbrain were mapped in the albino rat, using reducedsilver stains after lesions or the autoradiographic technique following injections of tritiated proline. In all major respects the two techniques gave the same results. The majority of the ascending projections sweep ventrally from the raphe nuclei, then curve rostrally to course through the ventral tegmentum and into the medial forebrain bundle (MFB). Others radiate through the mesencephalic reticular formation (RF) and central grey, turning ventrally at the posterior thalamic border to enter the subthalamus. From the MFB, fibers branch into the hypothalamus, preoptic areas, anterior amygdala and olfactory tubercle, while some fibers enter the fornix or the stria terminalis. Many fibers continue rostrally in the MFB, joining the diagonal bands of Broca to reach the septa1 nuclei or, further rostrally, the cingulum bundle. Fibers in the cingulum bundle turn caudally around the genu of the corpus callosum, some branching into the cell-free layers of the pregenual cortex. Running caudally, then curving around the splenium, the cinguIum bundle projection sprays out into the subiculum and in some cases a projection into the hippocampus is seen.Other ascending projections include one to the habenular nuclei through the fasciculus retroflexus. Projections to the mediodorsal, parafascicular and reuniens nuclei of the thalamus were also noted.Descending projections were observed to the dorsal tegmental nucleus and locus coeruleus and diffusely to the pontine reticular formation and caudal central grey. No projections were seen below the level of the facial nerve nucleus and none were observed to the cerebellum, caudal raphe nuclei or cranial nerve nuclei.Since the discovery that much of the serotonin in the brain is localized within the cell bodies, axons and axon terminals of a smaI1 group of nuclei in the midbrain tegmentum -the n. dorsalis raphe and n. medianus raphe (n. centralis superioris of Bechterew) -it has been suggested that those nuclei play important roles in mediating the effects of serotonin on sleep, neuroendocrine regulation, sexuality, aggression and pain responses (Chase and Murphy, '73 for review). However, though serotonin can be linked to these behaviors, the neuroanatomical pathways on which such functions are based have remained unclear. Earlier anatomical studies dealing with midbrain connections, such as those by Brodal and co-workers ('60) and Nauta and Kuypers ('58) either have used retrograde degeneration methods or have not focused systematically on the raphe. Numerous studies employing the histochemical fluorescence technique for serotonin (Dahlstrom and Fuxe, '65) have led to the proposal of an ascending serotonergic system presumably originating in the raphe nuclei of the midbrain (Anden et al., '66; Ungerstedt, '71). However, axons of cells containing serotonin can rarely be visualized and the fluorescence technique has appeared less sensitive f...

The dentate gyrus: fundamental neuroanatomical organization (dentate gyrus for dummies)

“…The serotonergic projection that originates from median and dorsal divisions of the raphe nuclei also terminates most heavily in the polymorphic layer in an immediately subgranular portion of the layer (Conrad et al, 1974;Moore and Halaris, 1975;Köhler and Steinbusch, 1982;Vertes et al, 1999). A number of GABAergic interneurons appear to be preferentially innervated by the serotonergic fibers.…”

Effects of pedunculopontine tegmental nucleus lesions on morphine-induced conditioned place preference and analgesia in the formalin test

“…Rather, forebrain structures appear to be responsible for t~e effect because lesions of the median raphe, which projects rostrally to forebrain structures (Conrad et al, 1974), have no effect on thü tail flick test Melzack, 1982: Buxbaum et al, 1973), but potentiate morphine analgesia in the formalin test (Abbott and Melzack, 1982). In addition, microinjections of morphine into the lateral ventricles (Cohen et al, 1984), lateral habenula, dorsal thalamic region (Cohen and Melzack, 1985), VTA and NA (Franklin, 1989;Morgan and Franklin, 1990) as weil as stimulation of the habenula (Cohen and Melzack, 1986) There is S0me evidence suggesting neural substrates mediating the reinforcing effects of drugs and analgesia in the formalin test overiap (Franklin, 1989;Lin et al, 1989).…”

Poster Communications

“…It is possible that activation of 5HT1iA cell body autoreceptors, in the raphe nuclei, could play a significant role in the effect observed (Invernizzi et al 1988). This hypothesis is supported by anatomical studies which have shown that 5HT-containing cells in this area project to both ends of the nigro-striatal dopamine system (Conrad et al, 1974 In an attempt to characterise the receptor subtypes involved, the effects of various 5-HT receptor ligands were investigated using this model. The 5-HT antagonist GR38032F ({Glaxo} 0.001-1.0 mg/kg i.p.…”