AMPA受容体トラフィッキングによる小脳シナプス活性の両方向性調節

抄録

Regulation of synaptic expression of AMPA type glutamate receptors (AMPA-Rs) through a receptor-trafficking is one of the underlying mechanism for synaptic plasticity in hippocampal and cerebellar neurons. In cerebellar Purkinje cell, induction of the long-term depression (LTD) of parallel fiber (PF)-EPSC requires clathrin-mediated endocytosis, however, relation between the constitutive rapid trafficking and LTD-induction was unclear. Suppressing exocytosis or endocytosis, we addressed whether regulation of the rapid constitutive trafficking of AMPA-Rs was underlying synaptic plasticity in cerebellar Purkinje cell. Effects of intracellular infusion of tetanus toxin (TeTx), a blocker of VAMP2, on PF-EPSC were analyzed in cerebellar slice using whole-cell patch-methods. Infusion of TeTx reduced amplitude of PF-EPSCs to 60% within 20 min. Since infusion of botulinum neurotoxin C (a blocker of syntaxin) reduced PF-EPSC amplitude to similar extent, contribution of TeTx-insensitive receptor-trafficking was suggested to be negligible. As a counterpart of constitutive elimination of synaptic AMPA-R, constitutive insertion of AMPA-Rs into PF-synapse was demonstrated by blocking of dynamin. As for relation between constitutive trafficking of AMPA-Rs and synaptic plasticity, LTD did not occlude with constitutive elimination of AMPA-Rs at PF-synapse, suggesting that internalization of synaptic AMPA-Rs during LTD did not belong to constitutively recycling pool of AMPA-Rs. [J Physiol Sci. 2006;56 Suppl:S19]