Molecular and cellular basis of synaptic function

本研究从三个方面探讨了突触传递的分子和细胞基础：1)受体通道的分子结构和电生理特性；2)钙代谢的调节及其与递质释放的关系；3)突触可塑性的机制。主要结果如下：1.受体通道的分子结构和功能特性Mishina通过cDNA的克隆和表达，鉴定了小鼠NMDA受体的四个调节亚基(epsilon1-epsilon4)。这种epsilon亚基的分子多样性是NMDA受体功能异质性的基础。小泽将膜片钳记录和逆转录结合后进行了PCR扩增，并在单细胞水平上鉴定了钙通透性AMPA受体的亚基组成。Takahashi表达了胎儿和成人型甘氨酸受体…，并表明成人型受体的平均打开时间较短的OP cDNA更多的时间。这一结果与甘氨酸能IPSCs的衰变时间在出生后的发育过程中变得更短是一致的。2.钙代谢和递质释放库巴测量了交感神经元细胞内钙离子浓度，并提出了钙诱导的钙释放激活是由于钙离子通过电压依赖性钙离子通道内流的结果。Yawo已经证明，通过N型钙通道的钙内流介导了鸡睫状突触前终末的递质释放。Tchibana证明了金鱼视网膜神经节细胞的递质是L-谷氨酸，这种递质的释放是由L型钙通道的激活所介导的。3.突触可塑性的机制平野研究了小脑颗粒与浦肯野细胞之间突触传递的长期抑制(LTD)的机制，提出证据表明代谢性谷氨酸受体(MGluR1)的激活参与了LTD的诱导。较少

In this study, we investigated molecular and cellular basis of synaptic transmission in the three aspects, namely 1)molecular structure and electrophysiological properties of receptor channels, 2)regulation of calcium metabolism and its relation to transmitter release, and 3)mechanism of synaptic plasticity. The main results are as follows.1.Molecular structure and functional properties of receptor channelsMishina has identified four modulatory subunits (epsilon1-epsilon4)of the mouse NMDA receptor by cloning and expression of cDNAs. This molecular diversity of the epsilon subunits underlies the functional heterogeneityb of the NMDA receptor. Ozawa has coupled patch-clamp recordings and reverse transcription followed by PCR amplification, and identified the subunit composition of the Ca^<2+>-permeable AMPA receptor at the single cell level. Takahashi has expressed fetal- and adult-type glycine receptor cDNAs, and shown that the mean open time of the adult-type receptor has a shorter op … More en time. This result is consistent with that the decay time of glycinergic IPSCs becomes shorter during postnatal development.2.Calcium metabolism and transmitter releaseKuba has measured intracellular Ca^<2+> concentration in sympathetic neurons and presented the evidence that the activation of calcium-induced calcium release occurs as a result of Ca^<2+>-influx through voltage-dependent Ca^<2+> channels. Yawo has shown that Ca^<2+>-influx through the N-type Ca^<2+> channel mediates transmitter release from the chick ciliary presynaptic terminal. Tachibana has demontrated that the transmitter of the ganglion cell of the goldfish retina is L-gluatamate, and that this transmitter release is mediated by the activation of L-type Ca^<2+> channels.3.Mechanism of synaptic plasticityHirano has investigated the mechanism of long-term depression (LTD) of the synaptic transmission between cerebellar granule and Purkinje cells, presenting the evidence that the adtivation of metabotropic glutamate receptor (mGluR1) is involved in the induction of LTD. Less