Mechanisms of Rapid Modulation of Auditory Responsiveness

听觉反应快速调节机制

• 批准号: 10055961
• 负责人: David McCormick
• 金额: $ 31.34万
• 依托单位: UNIVERSITY OF OREGON
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-12-01 至 2023-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10055961
• 关键词: Affect; Arousal; Attention; Auditory; Auditory area; Auditory system; Axon; Behavior; Behavioral; Brain; Caliber; Cells; Disease; Frequencies; Hippocampus (Brain); Individual; Inferior Colliculus; Injury; Knowledge; Measures; Medial; Medial geniculate body; Membrane Potentials; Methodology; Monitor; Movement; Neurons; Pathway interactions; Pattern; Property; Pupil; Recovery; Recovery of Function; Role; Signal Transduction; Slow-Wave Sleep; Structure; Synapses; Synaptic Potentials; System; Testing; Therapeutic; Time; Variant; Walking; Width; alertness; auditory processing; cholinergic; design; extracellular; hearing impairment; neuroregulation; noradrenergic; normal hearing; optogenetics; presynaptic; receptive field; response; sound

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.

概括 清醒状态的快速变化如何影响中枢听觉反应以及中枢听觉反应的作用是什么 去甲肾上腺素能和胆碱能系统？我们希望检验的中心假设是“快速调制 清醒状态的变化是由去甲肾上腺素能和胆碱能途径的活动变化引起的，并且发生 沿着一个连续体：1）由于皮质/皮质下自发性慢节律/低下而导致反应减少 频率细胞和网络在低唤醒期间爆发放电，2) 静止但准确响应的网络 在中等警觉性期间，以及3）由于高水平而在高唤醒或行走期间反应性降低 兴奋性和抑制性自发活动。鉴于听觉的调制，这是一个及时的话题 反应和处理不仅对正常听力很重要，而且对以下功能的恢复也很重要 损伤或疾病。在这里，我们将通过执行细胞外单元和 来自听觉皮层神经元和相关皮层下结构（内侧）的全细胞（突触）记录 膝状体、下丘）在清醒状态下精确测量的变化以及监测和 操纵上行胆碱能和去甲肾上腺素能通路的活性。这些结果共同将 显着增加了我们对正常细胞和网络机制的理解， 听觉皮层和皮层下功能的恢复。

项目成果

Decision-making dynamics are predicted by arousal and uninstructed movements.

决策动态是通过唤醒和无指导的运动来预测的。

• DOI: 10.1016/j.celrep.2024.113709
• 发表时间: 2024
• 期刊: Cell reports
• 影响因子: 8.8
• 作者: Hulsey,Daniel;Zumwalt,Kevin;Mazzucato,Luca;McCormick,DavidA;Jaramillo,Santiago
• 通讯作者: Jaramillo,Santiago