Serotonin and Synaptic Transmission in the Cerebellum
The neurotransmitter serotonin (5-hydroxytryptamine [5-HT]) is widely distributed in the central nervous system (CNS) and is involved in various physiological functions. In the cerebellum, serotonergic fibers are the third largest population of afferent f
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Fumihito Saitow, Moritoshi Hirono, and Hidenori Suzuki
Abstract
The neurotransmitter serotonin (5-hydroxytryptamine [5-HT]) is widely distributed in the central nervous system (CNS) and is involved in various physiological functions. In the cerebellum, serotonergic fibers are the third largest population of afferent fibers, innervating and affecting the functions of various regions. Although there are a number of studies showing that 5-HT influences activity of cerebellar circuitry, the physiological functions of 5-HT in the cerebellum remains largely unknown. This chapter will focus on the modulatory actions of 5-HT on synaptic transmission in the cerebellar cortex and deep cerebellar nuclei (DCN), which are key areas that play a role in cerebellar information processing. First, the literature describing 5-HT-mediated modulatory effects on glutamatergic and GABAergic synaptic transmission within individual cerebellar regions are reviewed. This article proposes that (1) 5-HT widely modulates the information flow from Purkinje cells in the cerebellar cortex, and (2) 5-HT facilitates the firing of DCN neurons directly, but it also suppresses synaptic transmission and the expression of long-term synaptic plasticity in DCN neurons. Finally, some developmental neurological disorders that may be attributed to malfunctions in the 5-HT system will be discussed.
F. Saitow (*) • H. Suzuki Department of Pharmacology, Nippon Medical School, Tokyo, 113-8602, Japan and Japan Science and Technology Agency, CREST, Tokyo, 102-0075, Japan e-mail: [email protected], [email protected] M. Hirono Laboratory for Motor Learning Control, RIKEN Brain Science Institute, Saitama, 351-0198, Japan e-mail: [email protected] M. Manto, D.L. Gruol, J.D. Schmahmann, N. Koibuchi, F. Rossi (eds.), 915 Handbook of the Cerebellum and Cerebellar Disorders, DOI 10.1007/978-94-007-1333-8_38, # Springer Science+Business Media Dordrecht 2013
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F. Saitow et al.
Introduction Serotonergic neuronal networks are among the earliest developing neurotransmitter systems in the mammalian brain (Lauder 1990) and eventually grow into the most widely distributed biogenic amine networks. In several regions of the brain, 5-HT is diffusely released by volume transmission and behaves as a neuromodulator rather than a neurotransmitter. These actions of 5-HT are believed to be important in the regulation of basic physiological functions, including circadian rhythms (Ursin 2002), nociception (Suzuki et al. 2004), and energy balance (Tecott 2007). 5-HT is also involved in higher brain functions such as cognition and emotions via modulation of synaptic plasticity (Sodhi and Sanders-Bush 2004; Ciranna 2006; Gonzalez-Burgos and Feria-Velasco 2008). 5-HT exerts its actions via 14 classes of receptors (Millan et al. 2008). With the exception of the 5-HT3 receptor, which is a cation-permeable ionotropic receptor, all 5-HT receptors are of the seven transmembrane-spanning, G-protein-coupled receptor (GPCR) type. Pharmacologically, these GPCRs are divided into two mai
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