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Physiological Reviews, Vol. 81, No. 3, July 2001, pp. 1143-1195
Copyright ©2001 by the American Physiological Society
Brain Science Institute, RIKEN, Wako, Saitama, Japan
Ito, Masao
Cerebellar Long-Term Depression: Characterization, Signal
Transduction, and Functional Roles. Physiol. Rev. 81: 1143-1195, 2001.
Cerebellar Purkinje cells
exhibit a unique type of synaptic plasticity, namely, long-term
depression (LTD). When two inputs to a Purkinje cell, one from a
climbing fiber and the other from a set of granule cell axons, are
repeatedly associated, the input efficacy of the granule cell axons in
exciting the Purkinje cell is persistently depressed. Section
I of this review briefly describes the history of research
around LTD, and section II specifies physiological characteristics of LTD. Sections III and IV
then review the massive data accumulated during the past two decades,
which have revealed complex networks of signal transduction underlying
LTD. Section III deals with a variety of first messengers,
receptors, ion channels, transporters, G proteins, and phospholipases.
Section IV covers second messengers, protein kinases,
phosphatases and other elements, eventually leading to inactivation of
DL-
-amino-3-hydroxy-5-methyl-4-isoxazolone-propionate-selective glutamate receptors that mediate granule cell-to-Purkinje cell transmission. Section V defines roles of LTD in the light
of the microcomplex concept of the cerebellum as functionally
eliminating those synaptic connections associated with errors during
repeated exercises, while preserving other connections leading to the
successful execution of movements. Section VI examines the
validity of this microcomplex concept based on the data collected from
recent numerous studies of various forms of motor learning in ocular
reflexes, eye-blink conditioning, posture, locomotion, and hand/arm
movements. Section VII emphasizes the importance of
integrating studies on LTD and learning and raises future possibilities
of extending cerebellar research to reveal memory mechanisms of
implicit learning in general.
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