The role of ion channels in shaping the function of inner ear neurons

摘要 前庭神经节神经元胞体表达多种离子通道。 和神经递质受体。这种多样性为以下方面提供了丰富的生物物理基础 塑造单个神经元的内在兴奋性并扩大群体的兴奋性 感官信号曲目。在前庭神经中，所需的时间精确度 编码快速头部运动是由神经元以不规则的间隔放电决定的， 而敏感地发现头部缓慢运动的能力是由神经元决定的 每隔一段时间就开火。在这里我们测试离子通道是否驻留在 前庭神经元膜产生了这种重要的多样性，或者其他 树突和突触形态的特化也是必要的。的决议案 这个问题需要离子通道组成和树枝状结构的联合表征。 单个神经元的形态。为了实现这一点，我们将进行膜片钳 记录结合单细胞标记在半完整神经上皮制备中的应用 其中神经元仍然与它们的毛细胞相连。两者之间的明确关系 离子通道的组成和神经元功能的建立不能不考虑 传出调制对单个离子通道的影响。利用药理学，我们 将定义胆碱能传出信号对两个离子通道的影响 突出控制前庭神经节的放电模式和兴奋性 神经元。我们将测试一些神经元是否比其他神经元更容易接受这种调制。 识别这种差异也可能揭示有选择性地瞄准目标的机会 针对特定神经元组的治疗学。我们将结合独一无二的联合 从我们的实验到离子通道和树枝状形态的表征 创建计算模型以检查离子通道的相对重要性 前庭传入反应的成分和树突整合。总体而言，我们的工作 集成了强大的计算和实验方法，以推进我们的 了解前庭功能的一个基本方面。

SUMMARY The cell bodies of vestibular ganglion neurons express a diverse range of ion channels and neurotransmitter receptors. This diversity provides a rich biophysical substrate for shaping the intrinsic excitability of individual neurons and expands the populations’ repertoire for sensory signaling. In the vestibular nerve, the temporal precision needed to code rapid head movements is determined by neurons firing at irregular intervals, whereas the ability to detect slow head movements sensitively is determined by neurons firing at regular intervals. Here we test whether the ion channels resident in the membranes of vestibular neurons produce this important diversity or whether other specializations of dendritic and synaptic morphology are also needed. The resolution of this question requires joint characterizations of ion channel composition and dendritic morphology in individual neurons. To provide this, we will perform patch-clamp recordings combined with single-cell labeling in semi-intact neuro-epithelium preparations in which neurons are still connected to their hair cells. Definitive relationships between ion channel composition and neuronal function cannot be established without considering the impact of efferent modulation on individual ion channels. Using pharmacology, we will define the impact of cholinergic efferent signals on two ion channels identified as being prominent for controlling the firing patterns and excitability of vestibular ganglion neurons. We will test if some neurons are more receptive to this modulation than others. Identifying such differences may also reveal opportunities for selectively targeting therapeutics to specific neuron groups. We will combine the unique joint characterizations of ion channels and dendritic morphology from our experiments to create computational models to examine the relative importance of ion channel composition and dendritic integration on vestibular afferent responses. Overall, our work integrates powerful computational and experimental approaches to advance our understanding of a fundamental aspect of vestibular function.