Information processing at auditory nerve synapses

声音是由耳蜗编码在听觉神经尖峰的时间。听觉神经纤维 通过被称为“赫尔德内球”的突触，汇聚到耳蜗核中的浓密细胞上。这 会聚导致由丛状细胞传递到高级听觉中心的定时信息的变化， 这可能影响声音定位和处理。实验表明， 细胞尖峰的大小受球内突触电流的影响很大，它受两个主要因素的影响。 影响体内。首先，当以正常速率激活时，球内突触表现出相当大的抑制。 第二，它们受到许多神经调节系统的影响。这两种影响都会影响 信息由浓密的细胞携带，但两者都没有得到很好的理解。该项目的具体目标是 确定（1）球内突触电流中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神经细胞的时间，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灌木细胞， 取自老鼠和沙鼠的脑切片。抑郁症的机制将首先考虑，通过测试 突触前囊泡耗竭和突触后受体脱敏和饱和的作用。 此外，一种不寻常的形式的抑郁症在endbulb将被检查，这已被提出， 涉及减少突触前钙内流，但从未直接测试过。也将确定 如何通过促进和激活NMDA受体来减轻抑郁症。此外，本发明还提供了一种方法， 电流钳和动态钳研究将测试高水平活动期间的延迟释放是否会破坏 丛状细胞的精确定时反应。这些研究将提供重要的 关于定时信息通过听觉的会聚而被转换的机制的信息 神经突触在现实的活动。 这项工作将研究耳蜗核细胞处理声音信息的机制。 它也将提供重要的见解功能的作用，不同的受体类型和 神经调节系统在神经元计算中起作用。这项工作可能会导致改善， 现有的耳蜗植入物和直接刺激耳蜗核的植入物。

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.