The Journal of Comparative Neurology 408:419-436 (1999)

Stimulation of the nucleus magnocellularis (NMC) of the medulla produces changes in locomotion, muscle tone, heart rate, and blood pressure. Glutamatergic input has been found to modulate muscle tone, whereas cholinergic input has been found to mediate cardiovascular changes produced by stimulation of the NMC. The current study was designed to identify the brainstem afferents to NMC by using retrograde transport of wheat germ agglutinin and horseradish peroxidase (WGA-HRP) combined with glutamate and choline acetyltransferase (ChAT) immunohistochemical and nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemical techniques. Fifty nanoliters of 2.5% WGA-HRP were microinjected into the NMC in the cat. A heavy density of WGA-HRP-labeled neurons was found in the ipsilateral mesencephalic reticular formation (MRF), periaqueductal gray, Kolliker-Fuse nucleus, and pontis centralis caudalis (PoC), in the contralateral pontis centralis oralis (PoO), and bilaterally in the nucleus paragigantocellularis lateralis. A moderate density of retrogradely labeled neurons was found in the ipsilateral side of the nuclei parvocellularis, retrorubral (RRN), PoO, and vestibular complex, in the contralateral PoC and nucleus gigantocellularis, and bilaterally in the inferior vestibular nucleus. Retrograde HRP/glutamatepositive cells could be found throughout the brainstem, with a high percentage in RRN, PoO, PoC, and MRF. Double-labeled WGA-HRP/ChAT neurons were found in the pedunculopontine nucleus. Double-labeled WGA-HRP/NADPH-d-positive neurons could be seen in many nuclei of the brainstem, although the number of labeled neurons was small. The dense glutamatergic projections to the NMC support the hypothesis that rostral brainstem glutamatergic mechanisms regulate muscle activity and locomotor coordination via the NMC, whereas the pontine cholinergic projections to the NMC participate in cardiovascular regulation. J. Comp. Neurol. 408:419-436, 1999. Published 1999 Wiley-Liss, Inc. Indexing terms: choline acetyltransferase; NADPH; sleep apnea; cardiovascular; locomotion; REM sleep Neurons in the nucleus magnocellularis (NMC) of the rostral ventromedial medulla have been shown to relate to electroencephalographic desynchronization (Moruzzi and Magoun, 1949), muscle atonia in rapid-eye-movement (REM) sleep (Siegel et al., 1979; Sakai et al., 1981), muscle tone suppression (Lai et al., 1987; Hajnik et al., 1995), and Re-locomotion (Noga et al., 1988; Atsuta et al., 1990; Perreault et al., 1993). By using the decerebrate cat model, we found that micromjection of non-N-methyl-Daspartate (non-NMDA) agonists and corticotropin-releasing factor (CRF) in NMC induces muscle atonia, whereas NMDA agonists induce muscle tone facilitation or locomotion (Lai and Siegel, 1988, 1991, 1992). Administration of NMDA into the nucleus gigantocellularis and ventralis of the rodent, Grant number: NSC83-0412-B-075A-033; Grant sponsor: Medical search service of the veterans Administration; Grant