PRESERVATION OF TIMING IN PLASTIC AUDITORY PATHWAYS

描述：(改编自《调查者摘要》)Hold的花萼 突触是电路中的一个关键元件，它被认为是计算声源的 哺乳动物听觉脑干的定位。行动的准确时间安排 来自这个突触的潜在输出是这项任务的中心，但机制 人们并没有很好地理解这种调节和保护产出的方式。在重复过程中 传入纤维刺激，这个突触遭受强大的突触抑制 这限制了它维持长期排放的能力。 第一个要检验的假设是，囊泡池的耗尽是主要的 这种短期形式的可塑性背后的因素。花萼的大小 终端允许人们同时膜片钳单个花萼终端和 突触后细胞，从而测量突触前钙电流和 诱发的EPSCs。目前，这个突触是大脑中唯一一个前 而突触后的录音可以同时进行。电压钳位协议 旨在引发最大突触前钙内流的设计将用于完全耗尽 可释放的囊泡池，并确定其大小和回收率。 因此，由囊泡池耗尽设置的动作电位输出的限制将 可定量测定。 第二个假设是谷氨酸转运体对 突触在高频下维持尖峰电位。的功能和运行轨迹 这个突触上的谷氨酸转运体是未知的。以确定他们的 函数，建议的工作将首先检查不同 突触前钙电流和EPSCs上的转运体拮抗剂。私家侦探计划 确定转运蛋白是否能阻止谷氨酸从突触“溢出” Cleft，进而阻止抑制钙电流的mGluR的激活 和EPSCs。转运体介导的电流在花冠，MNTB细胞， 或者周围的神经胶质细胞将决定转运蛋白的位置和时间 谷氨酸清除过程。 第三个假说是众多抑制性回合的激活 对MNTB神经元的输入显著改变了膜的兴奋性，因此， 单元格的峰值输出。通过独立激活bouton ipscs和 Calyceal EPSCs，他们计划确定 兴奋性和抑制性输入影响峰电位计时。的独特之处 突触允许系统地研究控制 并可能为突触特性如何适应提供新的见解 保持信息流通过听觉通路的时序。

DESCRIPTION: (Adapted from the Investigator's Abstract) The calyx of Held synapse is a key element in the circuitry that supposedly computes sound source localization in the mammalian auditory brain stem. Precise timing of action potential output from this synapse is central for this task but the mechanisms that modulate and preserve output is not well understood. During repetitive afferent fiber stimulation, this synapse suffers robust synaptic depression which limits its ability to sustain prolonged output of discharges. The first hypothesis to be tested is that vesicle pool depletion is the main factor behind this short-term form of plasticity. The large size of the calyx terminal allows one to simultaneously patch clamp a single calyx terminal and the postsynaptic cell, and thus, to measure presynaptic calcium currents and evoked EPSCs. Presently, this synapse is the only site in the brain where pre- and postsynaptic recordings can be made simultaneously. Voltage clamp protocols designed to elicit maximal presynaptic Ca influx will be used to fully deplete the releasable pool of vesicles, and to determine its size and recovery rate. The limit on action potential output, set by vesicle pool depletion, will thus be determined quantitatively. The second hypothesis is that glutamate transporters are critical for the synapse to maintain spikes at high frequencies. The function and locus of glutamate transporters at this synapse are unknown. To determine their function, the proposed work will examine first the effect of different transporter antagonists on presynaptic Ca currents and EPSCs. The PI plans to determine if transporters prevent glutamate "spillover" from the synaptic cleft, which in turn prevents the activation of mGluRs that inhibit Ca currents and EPSCs. Recordings of transporter mediated currents in the calyx, MNTB cell, or surrounding glia will then determine the locus of transporters and the time course of glutamate clearance. The third hypothesis is that activation of the numerous inhibitory bouton inputs onto MNTB neurons significantly alters membrane excitability, and thus, the spike output of the cell. By independently activating the bouton IPSCs and the calyceal EPSCs, they plan to determine how the interaction between excitatory and inhibitory inputs affects spike timing. The unique features of the synapse allow a systematic study of the underlying mechanisms that control spikes and may provide new insight into how synaptic properties adapt to preserve the timing of information flow through auditory pathways.