CELLULAR PHYSIOLOGY OF VESTIBULAR REFLEXES

前庭反射的细胞生理学

• 批准号: 2014770
• 负责人: BARRY W PETERSON
• 金额: $ 16.92万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-01-01 至 2001-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2014770
• 关键词: afferent nerve; calcium; ear pharmacology; excitatory aminoacid; glutamate receptor; laboratory mouse; mathematical model; model design /development; neural information processing; neural transmission; neuropharmacology; pharmacokinetics; receptor binding; tissue /cell culture; vestibular nerve; vestibular nuclei; vestibuloocular reflex; voltage /patch clamp; voltage gated channel

This project examines the cellular basis of signal transformations that occur in vestibular reflexes. Studies of the vestibuloocular reflex have revealed short and long-term multiplicative changes in reflex gain. Functional considerations suggest similar changes should occur in the vestibulocollic reflex. The principal aim of this project is to understand and quantitate the fundamental cellular mechanisms involved in such reflex modulations using an in vitro mouse brain slice preparation. We will study the electrophysiological and pharmacological properties of vestibular afferent input to medial vestibular nucleus (MVN) neurons in these slices. focusing on the kinetic behavior of the ionotrophic glutamate receptors (NMDA and AMPA) which underlie the synaptic currents elicited by repetitive (physiologic) activation of vestibular afferents. These studies will employ both whole-cell recordings of the synaptic currents, and excised patch recordings of single and macroscopic glutamate receptor-mediated currents. We will then study the modulation of this glutamatergic afferent input to vestibular nucleus neurons by cerebellar projections, examining the cellular mechanisms by which GABAergic cerebellar afferents sculpt the response of vestibular reflex interneurons to vestibular afferent inputs. Neuroanatomical labeling techniques will be used to reveal the projections of neurons that are studied so that we can relate our data to afferent activation and cerebellar modulation of speciflt- vestibuloocular and vestibulospinal reflexes. Data obtained from experimental portions of this study will then be used to generate models of vestibular signal processing in the MVN. which will provide key. insights into the neuronal substrates of signal transformations in these vestibular reflexes. Understanding of these reflexes is important since they are essential to maintain the clear vision and stable posture required to carry out many activities of daily living.

这个项目研究了信号转换的细胞基础， 出现在前庭反射中。对前庭-眼反射的研究有 揭示了反射增益的短期和长期乘性变化。 从功能上考虑，类似的变化应该发生在 前庭结肠反射。这个项目的主要目的是 了解并量化所涉及的基本细胞机制 在使用体外小鼠脑片进行的这种反射调制中 准备工作。我们将研究电生理学和药理学。 前庭传入前庭内侧核的特性 (MVN)神经元在这些切片上。主要关注的是 离子营养谷氨酸受体(NMDA和AMPA)是 重复(生理)激活的突触电流 前庭传入神经。这些研究将使用两种全细胞 突触电流的记录，以及切除的斑块记录 单一和宏观谷氨酸受体介导的电流。到时候我们会的 谷氨酸能传入对前庭的调制作用研究 核神经元通过小脑投射，检查细胞 GABA能小脑传入形成反应的机制 前庭反射中间神经元对前庭传入的反应。 神经解剖标记技术将被用来揭示 对神经元的投影进行研究，以便我们可以将我们的数据联系起来 对特异神经元的传入兴奋和小脑调制 前庭眼球和前庭脊髓反射。数据获取自 这项研究的实验部分将被用来生成模型 MVN的前庭信号处理。这将提供关键。 对这些细胞中信号转换的神经元底物的洞察 前庭反射。了解这些反应很重要，因为 他们对保持清晰的视野和稳定的姿势是必不可少的 需要进行许多日常生活活动。