Transneuronal Signals for Afferent Regulation

用于传入调节的跨神经元信号

• 批准号: 7418414
• 负责人: RICHARD L. HYSON
• 金额: $ 27.68万
• 依托单位: FLORIDA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-09-01 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7418414
• 关键词: Acoustic Nerve; Acoustic Stimulation; Acoustics; Address; Agonist; Apoptotic; Auditory; Auditory system; Biological Models; Brain; Brain Stem; Cannabinoids; Caspase; Cell Death; Cell Nucleus; Cell Survival; Cell physiology; Cells; Cessation of life; Chromosome Pairing; Class; Cochlea; Cochlear nucleus; Code; Condition; Data; Endocannabinoids; Event; Excision; Glutamates; Hearing Impaired Persons; In Vitro; Lead; Life; Ligands; Mediating; Metabotropic Glutamate Receptors; Methods; Modification; Molecular; Neurons; Neurosciences; Neurotransmitter Receptor; Physiological; Population; Preparation; Process; Production; Receptor Activation; Regulation; Research; Role; Signal Transduction; Slice; Stimulus; Synapses; Synaptic Transmission; System; Testing; Tissues; Variant; caspase-9; chemical function; deafness; in vivo; prevent; receptor; relating to nervous system; research study; synaptic function

One of the major themes in contemporary auditory neuroscience is activity-dependent modification of the brain. These activity-dependent changes can result from the cessation of neural activity as a result of deafness, or they can result from rapid, moment-to-moment changes in neural activity as the brain encodes the acoustic stimulus. This proposal looks at both forms of activity-dependent plasticity in the brain stem auditory system. First, deafness results in rapid changes in cochlear nucleus neurons and the eventual death of 20-30% of these neurons. The proposed research will test the hypothesis that activation of a class of neurotransmitter receptors, called metabotropic glutamate receptors, is both necessary and sufficient for preserving cochlear nucleus neurons following deafness. Hypotheses regarding the molecular cascade responsible for cell death following deafness will also be evaluated. Rapid activity-dependent plasticity in neural processing will also be evaluated in this same system. The proposed research will focus on a receptor known as the cannabinoid type 1 receptor. Substantial levels of this receptor appear to be present at the first synapse in the central auditory system (i.e., the synapse between the auditory nerve and the cochlear nucleus neuron), but little is known about its function in this system. The proposed studies will test hypotheses about what activation of this receptor does to neural activity in the cochlear nucleus, how the endogenous ligand for this receptor is produced, and why this receptor is useful for the coding of acoustic events. Together, these experiments will provide a broad understanding of the function of the chemical signals in the cochlear nucleus in both normal and deaf conditions.

当代听觉神经科学中的主要主题之一是活动依赖性修改 脑。这些与活动相关的变化可能是由于神经活动的停止而导致的 耳聋，或者它们可能是由于大脑编码神经活动的快速，瞬间变化而引起的 声刺激。该建议着眼于脑干中两种与活动相关的可塑性 听觉系统。首先，耳聋导致耳蜗神经元和最终死亡的快速变化 这些神经元中有20-30％。拟议的研究将检验以下假设 神经递质受体，称为代谢型谷氨酸受体，既需要且足够 耳聋后保留耳蜗核神经元。关于分子级联的假设 还将评估负责耳聋后细胞死亡的原因。快速活动依赖性可塑性 神经处理也将在同一系统中进行评估。拟议的研究将重点放在受体上 称为大麻素1型受体。该受体的大量水平似乎存在于第一 中央听觉系统中的突触（即听觉神经与耳蜗核之间的突触 神经元），但对其在该系统中的功能知之甚少。拟议的研究将检验有关的假设 该受体的激活对耳蜗核中的神经活性有什么作用，内源配体如何用于 产生该受体，以及为什么该受体可用于声音事件的编码。在一起，这些 实验将对耳蜗核中化学信号的功能提供广泛的理解 在正常和聋人条件下。