Firing patterns in vestibular afferents

前庭传入神经的放电模式

基本信息

批准号：
7486649
负责人：
RADHA KALLURI
金额：
$ 4.68万
依托单位：
MASSACHUSETTS EYE AND EAR INFIRMARY
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-12-01 至 2010-11-30
项目状态：
已结题

项目摘要

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.

描述（由申请人提供）：感官器官通常由不同的单元格类型填充，每种细胞类型都有允许其处理和传输不同信息模式的专业化。前庭传入神经元的发射模式的差异表明，前庭外围存在劳动分裂。根据其体内尖峰时序的规律性，哺乳动物前庭周围的传入神经元通常被描述为从高度规则到高度不规则。人们认为，这种射击模式的多样性反映了前庭外围编码感觉信息各个方面的能力。例如，认为不规则的神经元对于编码刺激的快速时间变化很重要，而常规神经元被认为对于编码较慢的变化很重要。尽管对体内头部运动的神经元反应进行了广泛的特征，但对这些射击模式的起源知之甚少。该提案的目标是使用电生理测量结果，再加上生物物理模型来识别支持点火模式差异所需的神经元专长。最近的体外研究表明，前庭传入神经元的somata表达了不同的离子电导群，这与早期模型一致，该模型提出前庭传入神经元的固有膜特性起着其能力的作用。为了在体外和体内特征联系起来，我建议通过在体外将伪突触刺激应用于前庭神经元，以表征神经元放电模式。为了研究它们对发射模式的影响，我将通过药理和动态夹具技术隔离电导。我将表征相关电导的动力学，并开发生物物理模型，以代表不同类别的前庭传入神经元的内在特性。这些模型将探讨固有膜特性的综合影响以及在塑造发射模式中收敛输入的数量和大小。通过结合新型刺激，动态夹具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性与体内数据功能功能相关的方法。拟议的研究重点是了解前庭神经元的电性能如何影响其携带感觉信息的能力。表征神经活动基础离子通道的体外研究对于了解这些通道中的遗传突变如何导致听力和平衡疾病至关重要。