CALCIUM CHANNELS AND INHIBITORY SYNAPTIC TRANSMISSION

描述：(摘自申请人的摘要)调制 电压依赖性钙通道调节神经递质的释放 可能是调节突触可塑性的一种常见机制。那里 目前关于钙通道控制的身份还没有达成共识 神经递质的释放，从而增加了不同 突触可能使用不同的通道类型。这项工程利用了这口井 海马区的特征化回路以研究其身份 控制特定抑制性突触释放的钙通道，以及 还有神经递质对这些通道的调节作用。抑制性 大脑皮层CA1区锥体细胞与垂直细胞之间的突触 东方层/肺泡，锥体层中的篮子细胞，以及 将对腔隙/分子层中的星状细胞进行研究。这个 垂直细胞和篮子细胞同时调节前馈抑制和重复性抑制 主要通过激活GABAA受体。星形调停 通过激活GABAB受体进行前馈抑制。第一个具体 目的是提供电压依赖性钙离子的完整特征。 这些突触的突触前细胞中的通道，使用完整的 分离细胞的电压钳记录。年获得的数据 这些实验将为后续的研究奠定基础。 神经递质的释放和钙通道的调节。第二 具体目的是确定哪种类型的钙通道控制释放 通过应用特定的钙通道，每个有问题的突触 突触后全细胞电压钳记录中的拮抗剂 海马片制备中的细胞。最终的具体目标是 确定钙离子流入量的减少是否可以解释 激活突触前GABAB产生的抑制性突触传递 和Mu阿片受体。GABA和阿片类药物对钙电流的影响 将研究用全电池电压钳记录在解离 垂直、篮状和星状中间神经元与特异性G细胞的参与 将探索这一过程中的蛋白质。了解如何 神经递质通过调制不同的基因来调节特定突触 钙通道的类型将提供对一些机制的洞察 突触可塑性。此外，这些研究将提供更好的 癫痫等疾病药物治疗基金会 神经退行性变，积极使用神经调节剂 被追捕。此外，这些信息还将提供对 突触功能不同神经元病的细胞病理学 是被更改的。

DESCRIPTION: (from applicant's abstract) Modulation of the voltage-dependent calcium channels regulating release by neurotransmitters is likely to be a common mechanism of regulating synaptic plasticity. There is currently no consensus on the identity of the calcium channel controlling neurotransmitter release, thus raising the possibility that different synapses may use different channel types. This project exploits the well characterized circuitry of the hippocampus to investigate the identity of calcium channels controlling release in specific inhibitory synapses, and also the modulation of these channels by neurotransmitter. The inhibitory synapses between the CA1 pyramidal cells and the vertical cells of the stratum oriens/alveus, the basket cells in the stratum pyramidale, and the stellate cells in the stratum laciunosum/moleculare will be studied. The vertical and basket cells mediate both feedforward and recurrent inhibition primarily by activation of GABAA receptors. The stellate mediate feedforward inhibition by activation of GABAB receptors. The first specific aim is to provide thorough characterization of the voltage-dependent calcium channels in the presynaptic cells of each of these synapses, using whole cell voltage-clamp recording in dissociated cells. The data obtained in these experiments will provide a foundation for the subsequent studies in neurotransmitter release and modulation of calcium channels. The second specific aim is to determine which calcium channel type controls release in each of the synapses in question, by application of specific calcium channel antagonists during whole cell voltage clamp recording in the postsynaptic cell in hippocampal slice preparation. The final specific aim is to determine if a decrease in calcium influx can account for the decrease of inhibitory synaptic transmission produced by activation of presynaptic GABAB and mu opioid receptors. The effect of GABA and opiates on calcium currents will be studied using whole cell voltage clamp recording in dissociated vertical, basket and stellate interneurons and the involvement of specific G proteins in this process will be explored. Understanding how neurotransmitter regulate specific synapses by modulation of distinct calcium channels types will provide insight into some of the mechanisms of synaptic plasticity. In addition, these studies will provide a better foundation for pharmaceutical therapies in diseases such as epilepsy and neurodegeneration where the use of neuromodulators is being actively pursued. Moreover, this information will also provide insights into the cellular pathology of various neuronal disorders in which synaptic function is altered.