Transneuronal Signals for Afferent Regulation

当代听觉神经科学的一个主要主题是活动依赖性的修饰

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.