Projections of the median raphe nucleus in the rat

Abstract

No previous report in any species has examined comprehensively the projections of the median raphe (MR) nucleus with modern tracing techniques. The present report represents an in depth analysis of the projections of MR by use of the anterograde anatomical tracer Phaseolus vulgaris‐leucoagglutinin. MR fibers descend along the midline within the brainstem and mainly ascend within the medial forebrain bundle in the forebrain. MR fibers distribute densely to the following brainstem/forebrain sites: caudal raphe nuclei, laterodorsal tegmental nucleus, dorsal raphe nucleus, interpeduncular nucleus, medial mammillary body, supramammillary nucleus, posterior nucleus and perifornical region of the hypothalamus, midline and intralaminar nuclei of thalamus, dopamine‐containing cell region of medial zona incerta, lateral habenula, horizontal and vertical limbs of the diagonal band nuclei, medial septum, and hippocampal formation. Virtually all of these structures lie on or close to the midline, indicating that the MR represents a midline/para‐midline system of projections. Overall, MR projections to the cortex are light. MR projects moderately to the perirhinal, entorhinal and frontal cortices, but sparingly to remaining regions of cortex. A comparison of MR with dorsal raphe (DR) projections (Vertes RP. 1991. J Comp Neurol 313:643–668) shows that these two major serotonin‐containing cell groups of the midbrain distribute to essentially nonoverlapping regions of the forebrain; that is, the MR and DR project to complementary sites in the forebrain. A direct role for the MR in the desynchronization of the electroencephalographic activity of the hippocampus and its possible consequences for memory‐associated functions of the hippocampus is discussed. J. Comp. Neurol. 407:555–582, 1999. © 1999 Wiley‐Liss, Inc.

Organization of Monosynaptic Inputs to the Serotonin and Dopamine Neuromodulatory Systems

“…On the other hand, although LHb projects strongly to DR (Vertes et al, 1999), we found that DR serotonin neurons (andVTA and SNcdopamine neurons) receive few monosynaptic inputs from LHb. Recent studies found that the rostromedial tegmental nucleus (RMTg)relays inputs from LHb to DR as well as to dopamine neurons (Jhou et al, 2009).…”

“…The reciprocal connection between DR and VTA hasbeen reported (Geisler and Zahm, 2005; Vertes et al, 1999) but which cell types contribute to these interactions is unknown. In particular, while serotonergicregulation of VTA dopamine neurons was confirmed by multiple methods (Boureau and Dayan, 2011), projectionsfrom dopamine to serotonin neurons have remained unclear(Ferreira et al, 2008; Kalén et al, 1988).…”

“…They are thought to be involved in diverse functions including the regulation of sleep-wake cycles(Lydic et al, 1983; McGinty and Harper, 1976), motor facilitation (Jacobs and Fornal, 1997), defensive behavior(Deakin and Graeff, 1991), behavioral inhibition (Soubrie, 1986), learning from negative reinforcement(Daw et al, 2002; Dayan and Huys, 2008; Deakin and Graeff, 1991; den Ouden et al, 2013), processing reward value(Nakamura et al, 2008; Seymour et al, 2012), andtemporal discounting(Doya, 2002; Miyazaki et al, 2011). Although it is known thatDR and MR project to overlapping, yet distinct forebrain structures(Azmitia and Segal, 1978; Vertes and Linley, 2008; Vertes et al, 1999), experimental manipulations in DR and MR have yielded equivocal results, and howserotonin neurons in these areasfunction remainselusive.…”

Activity of Raphé Serotonergic Neurons Controls Emotional Behaviors

“…Second, developmental SSRI exposure may differentially alter the establishment of specific inputs onto DR and MR 5-HT neurons (Dorocic et al, 2014; Lechin et al, 2006), including those from local GABAergic interneurons (Challis et al, 2013; Rood et al, 2014). Finally, MR and DR send reciprocal projections to each other (Bang et al, 2012; Muzerelle et al, 2014; Vertes et al, 1999), and developmental interference with the establishment of interconnectivity can lead to permanently altered relative 5-HTergic activity. Together these mechanisms might converge on permanently altering the balance between DR and MR 5-HTergic activity and provide a pathway for environmental and genetic factors to guide, influence or perturb 5-HTergic system development.…”

Review of the cytology and connections of the lateral habenula, an avatar of adaptive behaving

“…Retrograde labeling is detected in the raphe nuclei following injections of retrograde tracers into the LHb (Herkenham and Nauta, 1977; Li et al, 1993; Felton et al, 1999; Yetnikoff et al, 2015; Muzerelle et al, 2016) and strong bilateral projections from the median raphe to the LHb have been mapped by autoradiographic demonstration of anterogradely transported tritiated amino acids (Conrad and Pfaff, 1976a; Vertes and Martin, 1988) and PHA-L (Vertes et al, 1999). In contrast, Vertes (1991) was able to detect with PHA-L only a light ipsilateral projection to the LHb from the DR. Morin and Meyer-Bernstein (1999), studying the hamster, have made the interesting point that the MHb has a moderately dense serotonin terminal plexus, but does not receive significant input from the median or dorsal raphe, whereas LHb, which exhibits little serotoninergic immunoreactivity, receives substantial input from the raphe nuclei (mainly median raphe) presumably of a non-serotoninergic phenotype.…”