CALCIUM CHANNELS AND INHIBITORY SYNAPTIC TRANSMISSION

描述：（来自申请人的摘要） 电压依赖性钙通道通过神经递质调节释放 可能是调节突触可塑性的共同机制。 那里 目前还没有一致的身份的钙通道控制 神经递质的释放，从而提高了不同的可能性， 突触可以使用不同的信道类型。 这个项目利用了 海马体的特征电路，以研究 在特定抑制性突触中控制释放的钙通道，和 以及神经递质对这些通道的调节。 的抑制 CA 1锥体细胞和垂直细胞之间的突触 细胞层中的篮状细胞，以及 将研究腔隙层/分子层中的星状细胞。 的 垂直和篮状细胞介导前馈和复发抑制 主要通过激活GABAA受体。 星状细胞介导 通过激活GABAB受体的前馈抑制。 第一特定 目的是提供电压依赖性钙离子的彻底表征， 这些突触中的每一个的突触前细胞中的通道， 细胞电压钳记录在解离的细胞。 中获得的数据 这些实验为以后的研究奠定了基础， 神经递质的释放和钙通道的调节。 第二 具体目标是确定哪种钙通道类型控制在 通过应用特定的钙通道， 在突触后的全细胞电压钳记录过程中的拮抗剂 海马脑片制备。 最后的具体目标是 确定钙内流的减少是否可以解释 突触前GABAB激活产生的抑制性突触传递 和μ阿片受体。 GABA和阿片类药物对钙电流的影响 将使用分离的全细胞电压钳记录来研究 垂直，篮状和星状中间神经元和特定的G 蛋白质在这个过程中将被探索。 了解如何 神经递质通过调节不同的神经递质来调节特定的突触。 钙通道类型将提供一些深入了解的机制， 突触可塑性 此外，这些研究将提供更好的 基金会的药物治疗疾病，如癫痫和 神经变性，其中神经调节剂的使用被积极地 追求。 此外，这些信息还将提供有关 各种神经元疾病的细胞病理学，其中突触功能 被改变了

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.