Norepinephrine and Synaptic Transmission in the Cerebellum
Although the presence of norepinephrine (NE) in the mammalian cerebellum was initially controversial, there is now substantial evidence of a role for the NE system in modulating the response properties of individual cerebellar neurons to synaptic inputs r
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Daniel J. Chandler, Shevon E. Nicholson, Gerard Zitnik, and Barry D. Waterhouse
Abstract
Although the presence of norepinephrine (NE) in the mammalian cerebellum was initially controversial, there is now substantial evidence of a role for the NE system in modulating the response properties of individual cerebellar neurons to synaptic inputs rather than transmitting moment-to-moment details of modality specific information. As a result of these cellular actions, the system is capable of regulating cerebellar circuit functions within the context of ongoing voluntary and reflex motor activities and in a manner appropriate to the behavioral state of the organism. The evidence for this mode of operation derives from extensive anatomical, physiological, and pharmacological investigations over a period of more than 40 years. This chapter summarizes those studies and the development of this concept.
Introduction The presence of norepinephrine (NE) in the cerebellum and its role as a putative transmitter in this structure was debated for many years. After anatomical studies in the 1960s and 1970s demonstrated NE-containing fibers and terminals in the cerebellar cortex, attention was turned to the membrane actions of NE on individual cerebellar neurons and the net effect of NE release on cerebellar neuron and cerebellar circuit function. One of the confounding findings of early studies was that selective chemical lesion of NE fibers within the cerebellum or elsewhere in the brain failed to reveal any prominent sensory, motor, or behavioral
D.J. Chandler (*) • S.E. Nicholson • G. Zitnik • B.D. Waterhouse Department of Neurobiology and Anatomy, Drexel University College of Medicine, 2900 Queen Lane, Philadelphia, PA, 19129, USA e-mail: djc75@drexel.edu, Sen37@drexel.edu, gz34@drexel.edu, gz@drexel.edu, waterhouse@drexelmed.edu, bwaterho@drexelmed.edu M. Manto, D.L. Gruol, J.D. Schmahmann, N. Koibuchi, F. Rossi (eds.), 895 Handbook of the Cerebellum and Cerebellar Disorders, DOI 10.1007/978-94-007-1333-8_37, # Springer Science+Business Media Dordrecht 2013
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deficits in waking animals. Thus, despite evidence of the existence of NE fibers and demonstration of NE cellular effects, the role of the noradrenergic system in cerebellar function was not immediately obvious. Since that time, there have been numerous investigations that have gradually revealed a novel neuromodulatory action for NE within the cerebellum.
Anatomical Considerations Early fluorescent histochemical (Anden et al. 1967) and biochemical (Iversen and Glowinski 1966) studies provided the first evidence of NE-containing fibers within the cerebellar cortex. Later anatomical, physiological, and pharmacological experiments by Bloom et al. (1971), Hoffer et al. (1971a), and Siggins et al. (1971a) confirmed the existence of a prominent NE pathway from the brainstem nucleus locus coeruleus (LC) to all regions of the cerebellar cortex and deep cerebellar nuclei (Olson and Fuxe 1971; Segal et al. 1973; Mugnaini and Dahl 1975; Gould et al
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