Auditory Cortex: Synaptic organization and plasticity

听觉皮层：突触组织和可塑性

• 批准号: 8415558
• 负责人: Paul B Manis
• 金额: $ 35.46万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2016-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8415558
• 关键词: Acoustics; Action Potentials; Affect; Anisotropy; Area; Auditory Perception; Auditory area; Back; Basal Nucleus of Meynert; Biological Neural Networks; Brain; Calcium; Calcium Signaling; Cells; Cholinergic Receptors; Cochlear Implants; Computer Architectures; Data; Dendrites; Discrimination; Environment; Equilibrium; Exhibits; Exposure to; Foundations; Frequencies; Goals; Hearing; Hearing Aids; High-Frequency Hearing Loss; Lateral; Lead; Learning; Life; Maps; Measures; Mus; Muscarinic Acetylcholine Receptor; Neurons; Noise; Noise-Induced Hearing Loss; Optical Methods; Organ; Outcomes Research; Potassium Channel; Preparation; Process; Pyramidal Cells; Receptor Activation; Reporting; Research; Residual state; Self-Help Devices; Sensory; Sensory Process; Shapes; Slice; Source; Staging; Synapses; Synaptic plasticity; System; Testing; Thalamic structure; Time; Tinnitus; Voltage-Gated Potassium Channel; basal forebrain; base; cholinergic; classical conditioning; functional restoration; hearing impairment; hippocampal pyramidal neuron; in vivo; insight; neuromechanism; programs; public health relevance; relating to nervous system; research study; response; restoration; sensory system; sound

DESCRIPTION (provided by applicant): Sensory systems perform adaptive processing of the sensory environment on a moment-to- moment basis. In the cortex, adaptive processing develops the basic network, optimizes sensory learning for specific perceptual tasks, and supports compensatory responses to long- term changes in sensory input. Cortical plasticity depends on the organization of intracortical circuits as well as the intrinsic plasticity of local microcircuits. In this proposal, we will explore local circuit organization within and orthogonal to the tonotopic axes of the primary auditory cortex, the mechanisms regulating synaptic plasticity in those circuits, and the effects of hearing loss on circuit organization and synaptic plasticity. In the first aim, we will test the hypothesis that the organization of synaptic connections in L2/3 in primary auditory cortex is anisotropic with respect to the tonotopic axes, and we will compare the strength and organization of the supragranular input to L4 neurons with that from layers 5 and 6. We will measure the tonotopic map, then use a thalamocortical brain slice preparation to dissect the responses of morphologically identified neurons in physiologically defined regions to thalamic stimulation and to local intracortical stimulation, using a combination of electrophysiological and optical methods. In the second aim, we will examine cellular mechanisms that regulate a key trigger of synaptic plasticity, action potential back-propagation, in dendrites of L4 and L2/3 neurons. Stimulation of basal forebrain cholinergic systems has been shown to enhance map plasticity in vivo, and we find that activation of cholinergic receptors in auditory cortex affects spike timing-dependent plasticity. We will test the hypotheses that dendritic potassium channels regulate calcium signaling produced by back-propagating action potentials in dendrites, and that these channels are in turn regulated by muscarinic receptor activation. In the third aim we will test the hypothesis that noise-induced hearing loss increases synaptic connectivity between L2/3 pyramidal neurons in the normal-hearing region and the hearing- loss region, and that the hearing loss also decreases synaptic plasticity. Our experiments are aimed at identifying key circuits and cellular mechanisms that support adaptive processing functions at the initial stages of cortical processing, and to understand how those mechanisms respond to hearing loss.

描述（由申请人提供）：感觉系统在每时每刻的基础上执行感觉环境的自适应处理。在皮层，适应性处理发展了基本网络，优化了特定感知任务的感觉学习，并支持对感觉输入长期变化的补偿反应。皮质可塑性取决于皮质内回路的组织以及局部微回路的内在可塑性。在这个建议中，我们将探讨局部电路组织内和正交的初级听觉皮层的tonotopic轴，调节突触可塑性的机制，在这些电路，和听力损失的影响电路组织和突触可塑性。在第一个目标中，我们将测试的假设，在初级听觉皮层的L2/3的突触连接的组织是各向异性的tonotopic轴，我们将比较的强度和组织的颗粒上输入L4神经元从第5和第6层。我们将测量的tonotopic地图，然后使用丘脑皮质脑切片制备解剖的生理定义的区域，丘脑刺激和局部皮质内刺激，使用电生理学和光学方法相结合的形态学识别的神经元的反应。在第二个目标中，我们将研究在L4和L2/3神经元树突中调节突触可塑性的关键触发器，动作电位反向传播的细胞机制。基底前脑胆碱能系统的刺激已被证明可以增强体内地图的可塑性，我们发现，听觉皮层胆碱能受体的激活影响尖峰时间依赖的可塑性。我们将测试的假设，树突钾通道调节钙信号产生的反向传播动作电位在树突，而这些通道反过来又调节毒蕈碱受体激活。在第三个目标中，我们将测试噪声诱导的听力损失增加正常听力区域和听力损失区域中的L2/3锥体神经元之间的突触连接性，并且听力损失也降低突触可塑性的假设。我们的实验旨在确定在皮层处理的初始阶段支持自适应处理功能的关键电路和细胞机制，并了解这些机制如何对听力损失做出反应。