Mechanisms of Rapid Modulation of Auditory Responsiveness

摘要 觉醒状态的快速变化如何影响中枢听觉反应？ 去甲肾上腺素和胆碱能系统？我们希望检验的中心假设是“快速调制” 觉醒状态由去甲肾上腺素能和胆碱能通路的活动变化引起 沿着以下连续体：1)由于皮质/皮质下自发慢节律导致的反应减少/低 低唤醒期间的频率单元和网络突发激发，2)静态但准确响应的网络 在中等警觉性期间，以及3)由于高水平唤醒或行走时反应性降低 既有兴奋性也有抑制性自发活动。考虑到听觉调制，这是一个及时的话题 反应和加工不仅对正常听力很重要，而且对后续功能的恢复也很重要 损坏或疾病。在这里，我们将通过执行细胞外单位和 听皮层神经元和相关皮质下结构的全细胞(突触)记录(内侧 膝状、下丘)在准确测量清醒状态的变化期间以及监测和 调控胆碱能和去甲肾上腺素能上行通路的活性。总而言之，这些结果将 极大地增加了我们对正常和 听觉皮质和皮质下功能的恢复。

Summary How do rapid variations of the waking state influence central auditory responses and what is the role of noradrenergic and cholinergic systems? The central hypothesis that we wish to examine is “Rapid modulation of the waking state result from variations in activity of the noradrenergic and cholinergic pathways and occur along a continuum from: 1) reduced responses owing to cortical/subcortical spontaneous slow rhythms/low frequency cell and network burst firing during low arousal, 2) quiescent but accurately responsive networks during intermediate alertness, and 3) reduced responsiveness during high arousal or walking owing to high levels of both excitatory and inhibitory spontaneous activity. This is a timely topic, given that modulation of auditory responses and processing is important not only to normal hearing, but also in the recovery of function following damage or disease. Here we will test our central hypothesis (stated above) by performing extracellular unit and whole cell (synaptic) recordings from auditory cortical neurons and related subcortical structures (medial geniculate, inferior colliculus) during precisely measured variations in the waking state along with monitoring and manipulating the the activity of ascending cholinergic and noradrenergic pathways. Together, these results will yield a significant increase in our understanding of the cellular and network mechanisms of both normal, and recovery, of auditory cortical and subcortical function.