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Roles of Inhibitory Interneurons in the Cerebellar Cortex
Author(s) -
HIRANO TOMOO,
WATANABE DAI,
KAWAGUCHI SHINYA,
PASTAN IRA,
NAKANISHI SHIGETADA
Publication year - 2002
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2002.tb07583.x
Subject(s) - inhibitory postsynaptic potential , synaptic plasticity , chemistry , neuroscience , neurotransmission , synaptic fatigue , long term potentiation , nmda receptor , cerebellar cortex , gabaergic , cerebellum , microbiology and biotechnology , biology , excitatory postsynaptic potential , receptor , biochemistry
A bstract : The roles of inhibitory interneurons in the cerebellar cortex were investigated. First, Golgi cells were specifically eliminated in transgenic mice in which Golgi cells expressed human interleukin‐2 receptor α subunit (IL2Rα). Injection of exotoxin coupled to anti‐IL2Rα antibody in the cerebellum of the transgenic mouse eliminated Golgi cells and abolished GABA and synaptic inhibition in the granular layer. After elimination of Golgi cells, acute severe ataxia and subsequent mild motor discoordination were observed. In the latter chronic phase, NMDA receptor‐mediated synaptic response was reduced in granule cells. Our findings indicate that elimination of GABAergic inhibition in the granular layer caused overexcitation of granule cells resulting in severe ataxia, and then NMDA receptors in granule cells were downregulated, compensating for the reduction of GABAergic inhibition and improving motor control. In the second part, we report on the regulation mechanism of synaptic plasticity at inhibitory synapses on Purkinje cells (PCs). Inhibitory synaptic transmission on a PC is potentiated after repetitive PC depolarization. This synaptic plasticity (rebound potentiation, RP) was suppressed when a presynaptic neuron was activated during the PC depolarization. This synaptic regulation is unique in the sense that the homosynaptic activity suppresses the induction of synaptic plasticity. The mechanism of how presynaptic activity suppresses RP was examined. GABA released from the presynaptic terminal activated not only GABA A receptor but also GABA B receptor. The latter was coupled to Gi/o proteins, which downregulated adenylyl cyclase reducing cAMP and inactivated cAMP‐dependent protein kinase (PKA). Downregulation of PKA suppressed RP induction.