5‐HT5A receptor localization in the rat spinal cord suggests a role in nociception and control of pelvic floor musculature

Abstract

The 5-HT5A receptor is a seven-transmembrane receptor negatively coupled to adenylate cyclase, whose activation opens K+ channels. The 5-HT5A receptor may thus exert an inhibitory effect on neuronal activity. However, the function of this receptor is still largely unknown, in particular at the spinal level, and this is partly due to lack of specific ligands. Immunocytochemistry using specific anti-5-HT5A antibodies reveals a particularly dense labeling in the two superficial layers of the dorsal horn, suggesting that the 5-HT5A receptor may be involved in the spinal modulation of pain. In addition, a very intense staining in the lumbar dorsolateral nucleus (Onuf nucleus) in both males and females suggests that the 5-HT5A receptor is also involved in micturition through the control of urethral sphincter muscles. Colchicine pretreatment allows the staining of numerous cell bodies in lamina II. Fewer labeled cell bodies are seen in laminae I and III-VI, in the lateral spinal nucleus, and in lamina X. Electron microscope examination of 5-HT5A receptor immunoreactivity in spinal cords from untreated animals confirmed the postsynaptic labeling in all regions studied (dorsal horn, dorsolateral nucleus, and lamina X). The morphological heterogeneity of labeled dorsal horn cell bodies suggests that they belong to functionally distinct neurons (projection neurons and interneurons). In the lumbar dorsolateral nucleus, the labeling is preferentially localized on dendrites, suggesting that in this nucleus 5-HT preferentially acts at the dendritic level. Finally, the dense labeling of postsynaptic specializations suggests that the receptor may be in stock before being addressed to the synaptic differentiation.

Motor activity induces release of serotonin in the dorsal horn of the rat lumbar spinal cord

“…Several recent publications stress the role of 5-HT in modulation of motor activity, such as its role in control of pelvic musculature [3], its activation in the commissural region, its facilitatory effect on the activation of spinocerebellar tract neurons (in feline) [8] and, its increase in the effectiveness of pre-setting motor responses [9]. We show here that 5-HT release within the lumbar dorsal horn is increased during locomotor activity.…”

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AbstractLiterature highlights that serotonergic descending pathways [14] are implicated in somatosensory functions in the spinal cord and that serotonin (5-HT) in the dorsal horn might play a role in motor function through proprioceptive feedback [3,8,9,13]. We hypothesized that 5-HT release in dorsal horn might represent an important factor in the completion of locomotion by facilitation of the spinocerebellar tract [8] and/or by modulation of spinal reflex pathways [9].

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Serotonergic modulation of startle-escape plasticity in an African cichlid fish: a single-cell molecular and physiological analysis of a vital neural circuit

“…These results support a postsynaptic role of 5-HT in the M-cell and provide a great opportunity to learn more about the function of these receptors, given that their role in the vertebrate nervous system is still largely unclear. 5-HTR 5A has been associated with schizophrenia (Dubertret et al 2004) as well as bipolar disorder and major depression (Arias et al 2001), although its function is still only poorly understood (but see Doly et al 2004 for its potential role in the suprachiasmatic nucleus and Sprouse et al 2004 for nociception in the spinal cord). 5-HTR 6 has been implicated in anxiety, cognition, and the regulation of food intake (Woolley et al 2004); however, most of the evidence is still circumstantial.…”

Spatial and temporal patterns of serotonin release in the rat’s lumbar spinal cord following electrical stimulation of the nucleus raphe magnus

“…Monoamine release sites in the CNS are generally not located opposite postsynaptic receptors or membrane transporters (Descarries et al, 1990;Zhou et al, 1998;Doly et al, 2004). Solely on this anatomical basis, volume transmission has been proposed to be important in monoaminergic systems (Ridet and Privat, 2000;Vizi et al, 2004).…”

“…Although numerous functional and anatomical studies of the spinal serotonergic system and its brainstem origins have appeared, measurements of spinal serotonin release on temporal and spatial scales relevant to its extracellular dynamics have not been previously reported. A significant proportion of both serotonin receptors and membrane serotonin transporters are located remotely from release sites in the brain and spinal cord (Descarries et al, 1990;Zhou et al, 1998;Ridet and Privat, 2000;Doly et al, 2004). Thus extrasynaptic changes on scales of seconds and tenths of a millimeter are highly pertinent to serotonin's acute neurophysiologic actions, and are also a major consideration in designing therapies for transmitter replacement therapy in spinal cord injury.…”