Information processing at auditory nerve synapses

声音是在听觉神经的尖峰时刻由耳蜗编码的。听神经纤维 通过称为“Hold的终球”的突触汇聚到耳蜗核的浓密细胞上。这 会聚导致由丛生细胞传递到更高听觉中枢的定时信息发生变化， 这可能会影响声音定位和处理。实验已经表明，布希的定时 突触电流的大小很大程度上影响细胞的尖峰活动，而突触电流受两个主要因素的影响 在活体内的影响。首先，当以正常速率激活时，终球突触表现出相当大的抑郁。 其次，它们受制于许多神经调节系统。这两种影响都会影响 信息由浓密的细胞携带，但两者都没有被很好地理解。这个项目的具体目标是 确定(1)内球突触电流的使用依赖性变化的动力学和机制，(2) 突触电流的不同成分如何控制丛生细胞的计时，以及(3)神经调节如何 改变这些关系。这项工作将使用膜片钳记录的丛生细胞在 取自老鼠和沙土鼠的脑片。抑郁的机制将首先通过测试来考虑。 突触前小泡耗竭和突触后受体失敏与饱和的作用。 此外，还将检查末端球上一种不寻常的凹陷形式，这已被提议 包括减少突触前钙内流，但从未进行过直接测试。它也将被确定 如何通过促进和激活NMDA受体来缓解抑郁。此外, 电流和动态钳位研究将测试在高水平活动中断期间延迟释放 浓密细胞的精确定时响应。总而言之，这些研究将提供重要的 关于通过听觉会聚来转换定时信息的机制的信息 现实活动中的神经突触。 这项工作将研究耳蜗核细胞处理声音信息的机制。 它还将为不同受体类型和受体的功能作用提供重要的见解 神经调节系统在神经元计算中发挥作用。这项工作可能会在以下两方面带来改进 现有的人工耳蜗术和直接刺激耳蜗核的植入术。

Sounds are encoded by the cochlea in the timing of spikes in the auditory nerve. Auditory nerve fibers converge onto bushy cells in the cochlear nucleus, through synapses called "endbulbs of Held". This convergence leads to changes in the timing information passed on by bushy cells to higher auditory centers, which may affect sound localization and processing. Experiments have indicated that the timing of bushy cell spiking is greatly affected by the size of the endbulb synaptic current, which is subject to two major influences in vivo. First, endbulb synapses show considerable depression when activated at normal rates. Second, they are subject to a number of neuromodulatory systems. Both these influences can affect the information carried by bushy cells, but neither is well understood. The specific aims of this project are to determine (1) the dynamics and mechanisms of use-dependent changes in the endbulb synaptic current, (2) how the different components of the synaptic current control bushy cell timing, and (3) how neuromodulation changes these relationships. This work will be carried out using patch-clamp recordings of bushy cells in brain slices taken from mice and gerbils. The mechanisms of depression will be considered first, by testing the contributions of presynaptic vesicle depletion and postsynaptic receptor desensitization and saturation. In addition, an unusual form of depression at the endbulb will be examined, which has been proposed to involve reduced presynaptic calcium influx, but has never been directly tested. It will also be determined how depression could be mitigated by both facilitation and the activation of NMDA receptors. In addition, current- and dynamic-clamp studies will test whether delayed release during high levels of activity disrupts the precisely timed responses of bushy cells. Taken together these studies will provide important information about the mechanisms by which timing information is transformed by convergence of auditory nerve synapses during realistic activity. This work will examine the mechanisms used by cells in the cochlear nucleus to process sound information. It will also provide important insights into the functional role that different receptor types and neuromodulatory systems play in neuronal computation. This work may lead to improvements both in existing cochlear implants and in implants that stimulate the cochlear nucleus directly.