Firing patterns in vestibular afferents

描述（由申请人提供）：感觉器官通常由不同类型的细胞组成，每种类型的细胞都有专门的功能，可以处理和传输不同模式的信息。前庭传入神经元放电模式的差异表明前庭外围存在分工。哺乳动物前庭外周的传入神经元根据其在体内的峰值定时规律，通常被描述为从高度规则到高度不规则。这种放电模式的多样性被认为反映了前庭周围对不同方面的感觉信息进行编码的能力。例如，不规则神经元被认为对刺激中快速的时间变化进行编码，而规则神经元被认为对较慢的变化进行编码。尽管在体内对头部运动的神经元反应有广泛的描述，但对这些放电模式的起源知之甚少。这项建议的目标是使用电生理测量和生物物理模型来识别支持放电模式差异所需的神经元特化。最近的体外研究表明，前庭传入神经元的体体会表达不同类型的离子电导，这与早期提出的前庭传入神经元的内在膜特性在其发射不同类型动作电位的能力中起作用的模型一致。为了将体外和体内的表征联系起来，我建议通过对体外前庭神经元施加伪突触刺激来表征神经元放电模式。为了研究它们对放电模式的影响，我将用药理学和动态钳技术分离电导。我将描述相关电导的动力学特征，并开发生物物理模型来代表不同类别的前庭传入神经元的内在特性。这些模型将探讨在形成发射模式时，固有膜特性和收敛输入的数量和大小的综合影响。通过结合新的刺激、动态钳夹技术和生物物理模型，我们的实验将提供一种将特定离子电导的高质量生物物理特征与体内功能数据联系起来的方法。这项研究的重点是了解前庭神经元的电特性如何影响它们携带感觉信息的能力。体外研究表征神经活动下的离子通道对于理解这些通道中的基因突变如何导致听力和平衡障碍至关重要。

DESCRIPTION (provided by applicant): Sensory organs are often populated by different cell types, each of which has specializations that allow it to process and transmit different modes of information. Differences in the firing patterns of vestibular afferent neurons suggest that a division of labor exists in the vestibular periphery. Based on their in vivo spike timing regularity, afferent neurons of the mammalian vestibular periphery are commonly described as ranging from highly regular to highly irregular. This diversity of firing patterns is thought to reflect the vestibular periphery's ability to code different aspects of sensory information. For example, irregular neurons are believed to be important for coding fast temporal changes in the stimulus, whereas regular neurons are believed to be important for coding slower changes. Despite extensive characterizations of neuronal responses to head movements in vivo, little is known about the origin of these firing patterns. The goals of this proposal are to use electrophysiological measurements coupled with biophysical models to identify neuronal specializations that are needed to support differences in firing patterns. Recent in vitro studies show that the somata of vestibular afferent neurons express diverse groups of ionic conductances, consistent with an earlier model which proposed that a vestibular afferent neuron's intrinsic membrane properties plays a role its ability fire different patterns of action potentials. To link in vitro and in vivo characterizations, I propose to characterize neuronal firing patterns by applying pseudo-synaptic stimuli to vestibular neurons in vitro. To study their influence on firing patterns, I will isolate conductances pharmacologically and with dynamic clamp techniques. I will characterize the kinetics of the relevant conductances and develop biophysical models to represent the intrinsic properties of different classes of vestibular afferent neurons. The models will explore the combined influence of intrinsic membrane properties and number and size of converging inputs in shaping firing patterns. By combining novel stimuli, dynamic clamp techniques, and biophysical models, our experiments will provide a way to link high-quality biophysical characterizations of specific ion conductances to functional in vivo data. The proposed research is focused on understanding how the electrical properties of vestibular neurons affect their ability to carry sensory information. In vitro studies characterizing the ion channels underlying neural activity are crucial for understanding how genetic mutations in these channels can cause hearing and balance disorders.