Molecular Mechanism of Long-Term Plasticity at Cerebellar Inhibitory Synapses
The efficacy of synaptic transmission changes depending on the neuronal activity in the central nervous system. Such synaptic plasticity underlies experience-dependent refinement of information processing in a neuronal network, and is regarded as a cellular basis for learning and memory. Compared with excitatory synapses, little has been clarified about the regulatory mechanism of plasticity at inhibitory synapses. In this chapter, we summarize recent advances in understanding the molecular mechanism of inhibitory synaptic plasticity in the cerebellum. The GABAergic synapses on a Purkinje neuron undergo long-term potentiation of postsynaptic GABAA receptor (GABAAR) responsiveness in response to the postsynaptic depolarization, which is called rebound potentiation (RP). The mechanism of RP regulation has been studied at the molecular level using electrophysiological experiments combined with molecular biological techniques, fluorescent imaging and systems biological computer simulation. We here describe how the induction of RP is regulated through complicated interaction of intracellular signaling cascades including protein kinases/phosphatases, and how a GABAAR binding protein is implicated in the establishment and maintenance of inhibitory synaptic plasticity.
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