Abstract
Long-term depression of parallel fiber (PF) EPSC in Purkinje cell is considered as cellular basis for motor learning in the cerebellar cortex. This depression of PF-EPSC is caused by reduction in number of AMPA-receptor (AMPA-R) expressed at the postsynaptic membrane of PF-synapse by internalization of AMPA-R, which is suggested to be mediated through endocytosis in clathrin - dynamin dependent manner. Under normal condition, we found that AMPA-R surface expression was regulated by equilibrium between insertion and internalization of AMPA-R through constitutive exo- and endocytosis. For insertion of AMPA-R into PF-synapse membrane, NSF, an ATPase, is possibly involved in constitutive exocytosis since NSF-binding domain is reported in C-terminus of GluR2. To examine whether NSF is involved in constitutive exocytosis of AMPA-R in PF-synapse of cerebellar Purkinje cell, peptide of GluR2 C-terminal region (844-853), which was reported to block binding of NSF and GluR2 C-terminus region, applied through whole-cell patch-pipette to Purkinje cell in rat cerebellar slice. Results showed that this peptide (1mM) enhanced amplitude of PF-EPSC. NSF was suggested to be not involved in GluR2 insertion into PF-synapse through constitutive exocytosis. Since tetanus toxin (TeTX), a blocker of VAMP-mediated exocytosis, suppressed enhancement of PF-EPSC by this peptide, this peptide is suggested to suppress constitutive internalization, rather than constitutive insertion of GluR2 in PF-synapse. Binding of GluR2 and protein essential for internalization of GluR2 may be interfered by this peptide. [Jpn J Physiol 54 Suppl:S141 (2004)]
