Serotonergic innervations

Cobb W., Abercrombie E. (2003). Differential regulation of somatodendritic and nerve terminal release by serotonergic innervation of substantia nigra. J. 

Over the course of the last three decades, a variety of techniques have been used to characterize the circuitry of serotonergic neurons in the central nervous system. The density of serotonergic innervation in the forebrain was initially underestimated because the original histo-fluorescence method was limited in sensitivity and did not permit the detection of many fine axons and terminals. 

Subsequent anatomical techniques (e.g. immunohisto-chemistry of 5-HT or tryptophan hydroxylase, an enzyme unique to the synthesis of 5-HT retrograde and anterograde axonal transport studies) have allowed a more complete and accurate characterization of the serotonergic innervation of forebrain areas. 

Lesions of serotonergic neurons in laboratory animals have been reported by some, but not all, investigators to disrupt locomotor rhythms or to result in the loss of the daily rhythm of corticosterone. There is evidence that, in the hamster, the median raphe nucleus projects to the SCN whereas the dorsal raphe nucleus innervates the IGL furthermore, the serotonergic innervation to the SCN and not the IGL is necessary for the photic entrainment of locomotor activity [22]. It appears then, that the SCN circadian pacemaker or clock is modulated by stimulation of serotonergic receptors in the SCN and that serotonergic projections to the SCN may modulate the phase of the SCN in intact animals. 

Meyer-Bernstein, E. L. and Morin, L. P. Differential serotonergic innervation of the suprachiasmatic nucleus and the intergeniculate leaflet and its role in circadian rhythm modulation. J. Neurosci. 16 2097-2111,1996. 

Dluzen DE, Anderson LI, McDermott JL, Kucera J, Walro JM (2002) Striatal dopamine output is compromised within +/- BDNF mice. Synapse 43 112-117 Donovan SL, Mamounas LA, Andrews AM, Blue ME, McCasland JS (2002) GAP-43 is critical for normal development of the serotonergic innervation in forehrain. J Neurosci 22 3543-3552... 

Kosofsky BE, Molhver ME The serotonergic innervation of cerebral cortex different classes of axon terminals arise from dorsal and median raphe nuclei. Synapse 1 153-168, 1987... 

Mamounas LA, Wilson MA, Axt KJ, et al Morphological aspects of serotonergic innervation, in Serotonin, CNS Receptors and Brain Function (Advances in the Biosciences, Vol 85. Edited by Bradley PB, Handley SL, Cooper SJ, et al. Oxford, England, Pergamon, 1992, pp 97-118... 

Our recent immunocytochemical studies indicate that the 5-HT innervation of the cortex exhibits less interlaminar specificity than NE terminals and is, in general, complimentary to that of NE inputs (Fig. 27). The serotonergic innervation of PC is very heavy by comparison to DA and NE. 5-HT fibers are especially heavy in layers I and III and the endopiriform nucleus. The density of 5-HT fibers progressively decreases in the deeper parts of layer III. Layer II by contrast, is sparsely innervated. 5-HT fibers in all layers are relatively short, with a tortuous, convoluted orientation and exhibit more varicosities than NE or DA fibers. As with NE, there is little variation of 5-HT fiber distribution or density at different rostrocaudal levels of PC. 

As mentioned previously, serotonin has been shown to play a role in regulating brain growth [1]. Changes in serotonin synthesis, serotonergic innervation and serotonin receptor density may all influence brain development. 

The development of serotonergic innervation to the cerebral cortex has been characterized in neonatal rats by immunohistochemical techniques and autoradiographic imaging. These experiments demonstrate early serotonergic innervation that could be involved in a transient physiological role in sensory areas of the cortex or exert a trophic influence on the development of cortical circuitry and thalamocortical connections [76]. 

Monoamine oxidase A (MAOA) seems to be the principal serotonin degrading enzyme. The gene is located on chromosome Xpll [77]. Recent reports have shown that a low activity genetic variant of monoamine oxidase A (MAOA) is likely to be related to aggressive behavior, but only when paired with abusive experience in childhood. It also has been found that the low activity form of MAOA was associated with more adult symptoms of antisocial alcoholism than the high activity variant [113]. No studies related to autism have been carried out with this polymorphism (for more details see section 5 in Serotonergic innervations). 

The highly enriched expression of S-HTjc receptors on epithelial cells of the choroid plexus suggest a role in conveying serotonergic innervation to epithelial cell function. 

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