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.

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.

The effects of brainstem microinjections of carbachol on the hippocampal theta rhythm were examined in urethane anesthetized rats. The two most effective theta-eliciting sites with carbachol were the nucleus pontis oralis (RPO) and the acetylcholine-containing pedunculopontine tegmental nucleus (PPT) of the dorsolateral pontine tegmentum. RPO injections generated theta at mean latencies of 38.5 +/- 70.8 s and for mean durations of 12.9 +/- 5.1 min. Five of seven RPO injections gave rise to theta virtually instantaneously, i.e., before the completion of the injection. PPT injections generated theta at mean latencies of 1.7 +/- 1.1 min and for mean durations of 11.9 +/- 6.0 min. Injections rostral or caudal to RPO in the caudal midbrain reticular formation (RF) or the caudal pontine RF (nucleus pontis caudalis) generated theta at considerably longer latencies (generally greater than 5 min) or were without effect. Medullary RF injections essentially failed to alter the hippocampal EEG. The finding that theta was produced at very short latencies at RPO suggests that RPO, the putative brainstem source for the generation of theta, is modulated by a cholinergic input. The further demonstration that theta was also very effectively elicited with PPT injections suggests this acetylcholine-containing nucleus of the dorsolateral pons may be a primary source of cholinergic input to RPO in the generation of theta. The hippocampal theta rhythm is a major event of REM sleep. The present results are consistent with earlier work showing that each of the other major events of REM sleep, as well as the REM state, are cholinergically activated at the level of the pontine tegmentum.

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