|Budget Amount *help
¥12,000,000 (Direct Cost : ¥12,000,000)
Fiscal Year 1999 : ¥2,800,000 (Direct Cost : ¥2,800,000)
Fiscal Year 1998 : ¥4,000,000 (Direct Cost : ¥4,000,000)
Fiscal Year 1997 : ¥5,200,000 (Direct Cost : ¥5,200,000)
1.Excitatory postsynaptic potentials (EPSPs) were recorded in stratum radiatum of the CA1 region of the hippocampus by stimulating Schaffer collaterals. In order to determine the subtypes of glutamate receptors which are involved in the induction of long-term potentiation (LTP) of excitatory synaptic transmission, we first examined the effect of bath-applied NMDA on EPSPs. Although brief application of NMDA caused a transient synaptic potentiation, no LTP was induced. On the other hand, brief application of glutamate gave rise to LTP, suggesting an involvement of additional glutamate receptors other than NMDA receptors. 2.We next looked at the effect of ACPD, which is an agonist for metabotropic glutamate receptors (mGluRs), on EPSPs to examine a possibility that mGluRs are associated with LTP induction. Bath-application of ACPD caused only short-term depression, but failed to induce LTP. We obtained essentially the same results in whole-cell recordings from CA1 pyramidal cells. However, LTP was successfully induced when ACPD was applied in combination with depolarizing voltage pulses, which should activate postsynaptic voltage-dependent calcium channels. Thus, it is conceivable that LTP is induced only when mGluRs are activated concomitantly with an increase in postsynaptic calcium concentrations. In order to extend this study, we are currently generating gene-manipulated mice that express mGluR5 with a point mutation in its functional domain. 3.We found that presynaptic calcium-dependent protein kinases were involved in synaptic plasticity in the CA3 region of the hippocampus, whose induction was regulated by presynaptic mGluR2. For inducing long-term depression at the mossy fiber synapse in the CA3 region, activation of mGluRs was not sufficient, but calcium influx to the presynaptic terminal and subsequent regulation of biochemical processes were also required.