Biology Reference
In-Depth Information
GABAergic synapses on Purkinje cells, whereas Golgi cells inhibit activity of granule cells in
a feedback manner.
Around 1970, Marr and Albus proposed that the neural circuit in the cerebellar cortex can
be regarded as a three-layered perceptron [4,5]. A perceptron is a type of network system that
learns to distinguish input patterns. A three-layered perceptron consists of the sensory,
associative and output layers. Elements in the sensory layer send signals to elements in the
associative layer, and they in turn send signals to elements in the output layer. Information
processing in a perceptron is transformed by the teaching signal which tells whether the
output pattern of perceptron is appropriate or not. The efficacy of information transmission
between elements of the associative and the output layers is weakened if the output is
inappropriate, and strengthened if appropriate. Marr and Albus regarded mossy fibers as
elements in the sensory layer, granule cells as those in the associative layer and Purkinje cells
as those in the output layer (Figure 1). They thought that climbing fibers provide teaching
signals. Albus considered that climbing fibers code an error signal which is sent when the
output is inappropriate. It depresses the efficacy of synaptic transmission between parallel
fibers (granule cells) and a Purkinje cell, which occurred just before the arrival of error signal.
In the early 1980's, Masao Ito and his colleagues showed that conjunctive stimulation of
parallel fibers and a climbing fiber leads to long-term depression (LTD) of the information
transmission at the parallel fiber - Purkinje cell synapses [6].
The deep cerebellar nuclei (DCN) consist of the dentate, emboliform, globose and
fastigial nuclei. Neurons in DCN receive excitatory synaptic inputs from mossy and climbing
fibers, and inhibitory synaptic inputs from Purkinje cells. Some DCN neurons project to
premotor and motor areas of the cerebral cortex through the thalamus. Different functional
roles are assigned to the distinct regions of DCN. Some neurons in the vestibular nuclei also
receive synaptic inputs from Purkinje cells in the flocculus or in the ventral paraflocculus of
cerebellar cortex. Therefore, the cerebellar cortex participates in the neural computation
through modulation of outputs from DCN and vestibular nuclei.
In this chapter, we will first review the molecular mechanisms of LTD induction at
parallel fiber - Purkinje cell synapses. Then, we will introduce other forms of synaptic
plasticity in the cerebellum, and explain their implication in motor learning.
1.
L
ONG
-T
ERM
D
EPRESSION
The cerebellar LTD occurs at the parallel fiber - Purkinje cell synapses, when a Purkinje
cell receives concurrent synaptic inputs from parallel fibers and a climbing fiber [6-8]. It lasts
for more than 24 hours [9]. Both parallel and climbing fibers release glutamate as the
neurotransmitter. It is known that N-methyl-D-aspartate (NMDA) type of ionotropic
glutamate receptor plays an important role in the induction of synaptic plasticity in the
hippocampus [10]. However, the expression level of NMDA receptor is very low in mature
Purkinje cells [11,12]. Thus, implication of NMDA receptor in the cerebellar LTD is unlikely.
Major glutamate receptors on Purkinje cells are α-amino-3-hidroxy-5-
methylisoxazolpropionic acid (AMPA) type ionotropic glutamate receptor and type I
metabotropic glutamate receptor, mGluR1. The δ2 subunit of glutamate receptor is also
