Corollary Discharge Circuits in Auditory Cortex

听觉皮层的必然放电电路

基本信息

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
项目类别：
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

项目摘要

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）：大脑必须能够分离并区分我们自己的运动（重申刺激）引起的感觉与我们环境中物体（Exafferent刺激）引起的感觉。据信这是通过推论放电信号或投影到感官处理大脑区域的电机计划的副本发生的，从而抑制了重申的听觉感觉，以促进对听觉环境的准确感知。大量研究表明，推论排放电路的功能障碍，尤其是与试镜有关的电路，与使身体和精神障碍的衰弱有关，尤其是心理疾病的听觉幻觉特征。尽管在正常和患病的大脑中推论排出电路的重要性，但对于负责对听力很重要的推论排放信号的产生和传播的神经回路和突触机制知之甚少。 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.我将使用自定义在不受约束的运动和休息周期中，制作微型，电动微型训练以从听觉皮层中产生细胞内记录。我将使用突触后输入阻抗和神经元兴奋性的测试来检验以下假设：与运动相关的推论排放直接通过听觉皮层中的局部抑制来调节听觉皮质加工，这与皮质皮质形成模型一致。然后，我将使用光源操纵操纵来沉默一组运动皮质神经元的种群，这些神经元将其投射到听觉皮层上，以测试这些神经元负责推论放电信号的起源的假设。该项目的完成将详细说明一种突触和电路机制，该机制介导了听觉皮层中与运动相关的推论放电信号。