Transneuronal Signals for Afferent Regulation

当代听觉神经科学的主要主题之一是听觉系统的活动依赖性修饰。 个脑袋这些活动依赖性变化可能是由于神经活动的停止， 耳聋，或者它们可能是由于大脑编码时神经活动的快速，瞬间变化而引起的。 声刺激这项提议着眼于脑干中两种形式的活动依赖性可塑性 听觉系统首先，耳聋导致耳蜗核神经元的快速变化和最终死亡 20-30%的神经元。这项拟议中的研究将检验这样一个假设，即激活一类 神经递质受体，称为代谢型谷氨酸受体，是必要的和足够的， 耳聋后耳蜗核神经元的保存。关于分子级联的假说 也将评估导致耳聋后细胞死亡的原因。快速活性依赖性可塑性 神经处理也将在同一系统中进行评估。这项拟议中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存在于第一个 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），但对它在这个系统中的功能知之甚少。拟议中的研究将测试以下假设： 这种受体的激活对耳蜗核的神经活动有什么影响， 这种受体的产生，以及为什么这种受体对编码声音事件有用。所有这些 实验将提供对耳蜗核中化学信号功能的广泛理解 在正常和失聪的情况下。

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.