Dorsal raphe

ACh is widely distributed throughout the brain and parts of the spinal cord (ventral horn and dorsal columns). Whole brain concentrations of lOnmolg" tissue have been reported with highest concentrations in the interpeduncular, caudate and dorsal raphe nuclei. Turnover figures of 0.15-2.0 nmol g min vary with the area studied and the method of measurement, e.g. synthesis of labelled ACh from [ " C]-choline uptake or rundown of ACh after inhibition of choline uptake by hemicholinium. They are all sufficiently high, however, to suggest that in the absence of synthesis depletion could occur within minutes. 

B6 and B7 Dorsal Raphe nucleus B1 and B4 Nucleus Raphe pallidus... 

Lowry, CA, Odda, JE, Lightman, SL and Ingram, CD (2000) Corticotropin-releasing factor (CRF) increases the in vitro firing rates of serotonergic neurones in the rat dorsal raphe nucleus evidence for selective activation of a topographically organised mesolimbocortical system. J. Psychopharmacol. 14 (Suppl 2) All. 

Of course, cholinergic neurons are not the only ones with axon terminals in the cortex and if their degeneration does originate in the cortex then other afferants and their neurons could also be affected. This contention is supported by reported reductions in the number of NA neurons in the locus coeruleus, and 5-HT neurons in dorsal raphe but these are less marked (approximately 50%) than the loss of cholinergic neurons. Accompanying reductions in cortical NA and 5-HT are also seen but are again lower than those for ChAT but 5-HT2 receptors are reduced (43%). 

Figure 22.8 The distribution of brainstem Raphe nuclei. Neurons that release 5-HT are clustered in two groups of nuclei in the pons and upper brainstem. The superior group, which projects to forebrain areas, includes the dorsal Raphe nucleus (DRN) and the median Raphe nucleus (MRN). The inferior group projects to the medulla and spinal cord and includes the nucleus Raphe pallidus (NRP), the nucleus Raphe obscurus (NRO) and the nucleus Raphe magnus (NRM)...

Rebee, G.V., and Curtis, S.D. Reciprocal changes in the firing rate of the neostriatal and dorsal raphe neurons following loeal infusions or systemic injections of f-amphetamine Evidence for neostriatal heterogeneity. 

Rebec, G.V. Curtis, S.D. and Zimmerman, K.S. Dorsal raphe neurons Self-inhibition by an amphetamine-induced release of endogenous serotonin. Brain Res 251 374-379, 1982. 

Azmitia, E.C. The serotonin-producing neurons of the midbrain median and dorsal raphe nuclei. In Iversen, L.L. Iversen, S.D. and Snyder, S.H.. eds. Handbook of Psychopharmacology. Vol. 9. New York Plenum Press, 1978. pp. 233-314. 

Conrad, L.C.A. Leonard, C.M. and ffaff, D.W. Connections of the median and dorsal raphe nuclei in the rat Autoradiographic and degeneration study. J Comp Neurol 156 179-206. 1974. 

Jacobs, B.L. Foote, S.L. and Bloom, F.E. Differential projections of neurons within the dorsal raphe nucleus of the rat A horseradish peroxidase (HRP) study. Brain Res 147 149-153, 1978. 

Kombian SB, Reiffenstein RJ, Colmers WF. 1993. The actions of hydrogen sulfide on dorsal raphe serotonergic neurons in vitro. J Neurophysiol 70 81-96. 

Guzman-Marin, R., Alam, Md. N., Szymusiak, R. et al. (2000). Discharge modulation of rat dorsal raphe neurons during sleep and waking Effects of preoptic/basal forebrain warming. Brain Res. 875, 23-34. 

Nitz, D. Siegel, J. (1997a). GABA release in the dorsal raphe nucleus role in the control of REM sleep. Am. J. Physiol. 273, R451-5. 

Peyron, C., Petit, J.-M., Rampon, C., Jouvet, M., Luppi, P.-H. (1998). Forebrain afferents to the rat dorsal raphe nucleus demonstrated by retrograde and anterograde tracing methods. Neuroscience 82, 443-68. 

Noradrenaline acts on three types of receptor. The ai receptors mediate the main excitatory effects of noradrenaline upon wake-active neurons in the dorsal raphe, basal forebrain, and elsewhere (Vandermaelen Aghajanian, 1983 Nicoll, 1988 Fort et al., 1995 Brown et al., 2002). The a2 receptors mediate inhibitory effects of noradrenaline, e.g. on noradrenaline neurons themselves and on cholinergic brainstem neurons (Williams et al., 1985 Williams Reiner, 1993). The (3-receptors modulate neurons in a more subtle fashion, increasing excitability via blockade of afterhyperpolarizations in hippocampal and cortical neurons (Haas Konnerth, 1983). Activation of (3-receptors also promotes synaptic plasticity via activation of the cyclic-AMP-dependent kinase (PKA) and cyclic AMP response element binding protein (CREB) signal transduction pathway (Stanton Sarvey, 1987 Cirelli et al., 1996). 

Figure 2.4 Flip-flop switch model of wake and slow wave sleep active systems. Mutually inhibitory connections exist between GABAergic/Galaninergic slow wave sleep active neurons in the ventrolateral preoptic area (VLPO) of the anterior hypothalamus and aminergic neurons in the hypothalamus (histamine (HA) neurons in the tuberomammillary nucleus (TMN)) and brainstem (serotonin (5-HT) neurons in the dorsal raphe (DR) and noradrenaline (NA) neurons in the locus coeruleus (LC)). Orexinergic neurons in the perifornical hypothalamus (PFH) stabilize the waking state via excitation of the waking side of the flip-flop switch (aminergic neurons).

Brown, R. E., Sergeeva, O. A., Eriksson, K. S. Haas, H. L. (2002). Convergent excitation of dorsal raphe serotonin neurons by multiple arousal systems (orexin/hypocretin, histamine and noradrenaline). J. Neurosci. 22, 8850-9. 

Gervasoni, D Peyron, C., Rampon, C., et al (2000). Role and origin of the GABAergic innervation of dorsal raphe serotonergic neurons. J. Neurosci. 20, 4217-25. 

Lydic, R., McCarley, R. W. Hobson, J. A. (1987). Serotonin neurons and sleep. II. Time course of dorsal raphe discharge, PGO waves, and behavioral states. Arch. Ital. Biol. 126, 1-28. 

---