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.

当代听神经科学的主要主题之一是活动依赖的调节 大脑。这些依赖活动的变化可能是由于以下原因导致的神经活动停止 耳聋，或者它们可能是由于大脑编码大脑活动时神经活动的快速、每时每刻的变化造成的 声学刺激。这一建议着眼于脑干活动依赖可塑性的两种形式。 听觉系统。首先，耳聋会导致耳蜗核神经元的快速变化，最终导致死亡 这些神经元的20%-30%。这项拟议的研究将检验这样一种假设，即一类基因的激活 神经递质受体，称为代谢性谷氨酸受体，对 耳聋后保留耳蜗核神经元。关于分子级联的假说 也将对耳聋后细胞死亡的责任进行评估。快速活度相关塑性 神经处理也将在这个相同的系统中进行评估。拟议的研究将集中在一种受体上。 被称为大麻素1型受体。这种受体的大量水平似乎在第一阶段就存在。 中枢听觉系统中的突触(即听神经和耳蜗核之间的突触 神经元)，但对其在该系统中的功能知之甚少。拟议中的研究将检验关于 这种受体的激活对耳蜗核的神经活动有什么影响，内源性配体是如何 这种受体是产生的，以及为什么这种受体对声学事件的编码有用。加在一起，这些 实验将使我们对化学信号在耳蜗核中的功能有更广泛的了解。 在正常和失聪的情况下。