The role of metabotropic glutamate receptors in long-term potentiation of hippocampal synaptic transmission

1.通过刺激Schaffer络，记录海马CA1区辐射层的兴奋性突触后电位（EPSPs）。为了确定参与兴奋性突触传递的长时程增强（LTP）诱导的谷氨酸受体亚型，我们首先检测了浴用NMDA对epsp的影响。虽然短暂应用NMDA可引起短暂的突触增强，但未引起LTP。另一方面，谷氨酸的短暂应用引起了LTP，这表明除了NMDA受体外，还有其他谷氨酸受体参与。2.接下来，我们研究了代谢性谷氨酸受体（mGluRs）的激动剂ACPD对epsp的作用，以研究mGluRs与LTP诱导相关的可能性。ACPD浴敷仅引起短期抑郁，未引起LTP。我们在CA1锥体细胞的全细胞记录中获得了基本相同的结果。然而，当ACPD与去极化电压脉冲联合应用时，LTP被成功诱导，去极化电压脉冲应该激活突触后电压依赖性钙通道。因此，可以想象，LTP只有在mglur被激活并伴随突触后钙浓度增加时才会被诱导。为了扩展这项研究，我们目前正在培养表达mGluR5功能域点突变的基因操纵小鼠。3.我们发现突触前钙依赖性蛋白激酶参与海马CA3区的突触可塑性，其诱导受突触前mGluR2调控。为了在CA3区域诱导苔藓纤维突触的长期抑制，mGluRs的激活是不够的，但钙流入突触前末端和随后的生化过程调节也是必需的。

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.