Corollary Discharge Circuits in Auditory Cortex

听觉皮层的必然放电电路

• 批准号: 8717134
• 负责人: ANDERS NELSON
• 金额: $ 4.27万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8717134
• 关键词: Animals; Auditory; Auditory Hallucination; Auditory Perception; Auditory area; Axon; Behavior; Behavioral; Brain; Brain region; Characteristics; Custom; Disease; Environment; Esthesia; Functional disorder; Generations; Grooming; Health; Hearing; Ion Channel; Light; Link; Locomotion; Measurement; Measures; Mediating; Mental disorders; Methods; Modeling; Monitor; Motor; Motor Cortex; Movement; Mus; Neurons; Physiological; Population; Process; Psychotic Disorders; Research; Resolution; Rest; Schizophrenia; Sensory; Sensory Process; Series; Signal Transduction; Source; Stimulus; Symptoms; Synapses; Techniques; Testing; Thalamic structure; Viral; electric impedance; innovation; insight; nervous system disorder; neural circuit; neuronal excitability; optogenetics; postsynaptic; public health relevance; research study; response; vocalization

DESCRIPTION (provided by applicant): The brain must be able to separate and distinguish sensations arising from our own movements (reafferent stimuli) from those arising from objects in our environment (exafferent stimuli). This is believed to occur via a corollary discharge signal or a copy of the motor plan projected onto sensory processing brain regions, that suppress reafferent auditory sensations to facilitate accurate perception of the auditory environment. A large body of research indicates that dysfunction of corollary discharge circuits, particularly those related to audition, is linked to debilitating physical and mental disorders, notably the auditory hallucinations characteristic of psychoses. Despite the importance of corollary discharge circuits in the normal and diseased brain, remarkably little is known about the neural circuits and synaptic mechanisms responsible for the generation and propagation of corollary discharge signals important to hearing. Here I propose a series of innovative physiological, optogenetic, and behavioral experiments in mouse to measure and identify corollary discharge signals related to naturalistic behaviors including vocalization, grooming, and locomotion, and to test the hypothesis that specific populations of motor cortical neurons that send axon collaterals to the auditory cortex are the source of these corollary discharge signals. I will utilize a custom make miniature, motorized microdrive to make intracellular recordings from the auditory cortex during unrestrained movements and periods of rest. I will use tests of postsynaptic input impedance and neuronal excitability to test the hypothesis that movement-related corollary discharge directly modulates auditory cortical processing through local inhibition in the auditory cortex, consistent with a cortico-cortical model of corollary discharge. I will then use optogeneti manipulation to silence a population of motor cortical neurons that projects to the auditory cortex, testing the hypothesis that these neurons are responsible for the genesis of a corollary discharge signal. Completion of this project will detail a synaptic and circuit mechanism that mediates movement-related corollary discharge signals in the auditory cortex.

描述（由申请人提供）：大脑必须能够将我们自己的运动（传入刺激）引起的感觉与我们环境中的物体（外传入刺激）引起的感觉分开并区分开来。这被认为是通过投射到感觉处理脑区域的必然放电信号或运动计划的副本发生的，其抑制传入听觉以促进对听觉环境的准确感知。大量研究表明，必然放电回路的功能障碍，特别是与听觉有关的功能障碍，与使人衰弱的身体和精神障碍有关，特别是精神病特有的幻听。尽管推论放电回路在正常和患病大脑中的重要性，但对负责产生和传播对听力重要的推论放电信号的神经回路和突触机制知之甚少。在这里，我提出了一系列创新的生理学，光遗传学和行为实验小鼠测量和识别相关的自然行为，包括发声，梳理，和运动的必然放电信号，并测试的假设，即特定群体的运动皮层神经元，发送轴突侧支到听觉皮层是这些必然放电信号的来源。我会利用一个习惯 制作微型电动微驱动器，在无限制的运动和休息期间从听觉皮层进行细胞内记录。我将使用突触后输入阻抗和神经元兴奋性的测试来测试的假设，运动相关的推论放电直接调制听觉皮层的处理，通过在听觉皮层的局部抑制，符合皮质-皮质模型的推论放电。然后，我将使用optogeneti操纵沉默的运动皮层神经元的人口，项目的听觉皮层，测试的假设，这些神经元负责的起源的必然放电信号。本计画完成后，将详细说明听觉皮质中介导与运动相关的必然放电讯号的突触与回路机制。