Abstract
At the GABAergic synapses between an inhibitory interneuron and a Purkinje neuron (PN) in the cerebellum, postsynaptic depolarization results in long-lasting potentiation of the transmission efficacy (rebound potentiation: RP). We previously demonstrated that presynaptic activation coupled with postsynaptic depolarization suppresses the induction of RP through activation of postsynaptic GABAB receptors. Here we show that the suppressive effect of GABABR activation during depolarization of PNs on the RP induction is not transient but sustained for more than 4 days through augmentation of the integrin-mediated intracellular signaling. Five minutes conditioning treatment of cultured cerebellar neurons with the solution containing 50 mM of KCl and baclofen, a selective GABABR agonist, suppressed the RP induction for more than 72 hours. This long-lasting suppression of RP (LSRP) was blocked either by inhibition of de novo transcription using actinomycin D or by inhibition of MAPK cascades with either U0126 or PD98059 during the conditioning treatment. Thus, the establishment of LSRP depends on the de novo transcription and MAPK cascades. LSPR was abolished by inhibition of integrins using GRGDSP peptide, a competitive inhibitor of integrin binding to ligand proteins. Function blocking antibody against either integrin α3 or β1 subunits also abolished the LSRP, suggesting that the LSRP is mediated by the integrin α3/β1 heterodimer. We also present data suggesting that src-family of protein tyrosine kinases mediates the LSRP downstream of integrins. [Jpn J Physiol 54 Suppl:S142 (2004)]
