Corticofugal Circuits for Active Listening

积极倾听的皮质回路

• 批准号: 10350654
• 负责人: Daniel B. Polley
• 金额: $ 41.02万
• 依托单位: MASSACHUSETTS EYE AND EAR INFIRMARY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-03-01 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10350654
• 关键词: Active Listening; Adaptive Behaviors; Address; Anatomy; Animals; Attention; Attention deficit hyperactivity disorder; Auditory; Auditory Perception; Auditory Perceptual Disorders; Auditory area; Awareness; Axon; Behavior; Behavioral; Brain; Brain Stem; Cell Nucleus; Cells; Cerebral cortex; Code; Cognitive; Cues; Decision Making; Detection; Development; Electrophysiology (science); Environment; Genetic; Hyperacusis; Image; In Vitro; Learning; Measurement; Measures; Medial geniculate body; Methods; Midbrain structure; Monitor; Morphology; Motor; Mus; Neurons; Output; Pattern; Perception; Performance; Physiology; Play; Probability; Process; Property; Publishing; Regulation; Reporting; Research; Rodent; Role; Schizophrenia; Sensory; Shapes; Signal Transduction; Slide; Source; Synapses; System; Testing; Thalamic structure; Time; Tinnitus; Training; Visual; auditory nuclei; auditory processing; auditory stimulus; awake; cell type; cellular imaging; excitatory neuron; expectation; experimental study; follow-up; improved; in vivo; inhibitory neuron; neural circuit; neurophysiology; optogenetics; relating to nervous system; response; sensory cortex; sound; spatiotemporal

Project Summary During active listening, sound features that are distracting, irrelevant, or totally predictable are suppressed and do not rise to perceptual awareness. By contrast, inputs selected for amplification convey behaviorally relevant auditory signals used to guide ongoing perceptual decision making. The neural circuit mechanisms that selectively suppress or amplify bottom-up inputs to support active listening remain largely mysterious. Logically, neurons that support active listening would have inputs from cognitive signals that encode expectation, attentional selection and task demands, yet would also be able to adjust the gain and tuning of low-level auditory neurons that encode or compute bottom-up sound features. The massive network of descending auditory corticofugal neurons fit the bill because their cell bodies are embedded in highly plastic centers for cortical sound processing, yet their axons innervate subcortical auditory nuclei in the thalamus, midbrain and brainstem. Addressing the involvement of corticofugal neurons in active listening behaviors has been challenging due to the technical difficulty of isolating and manipulating specific classes of auditory cortex neurons in awake, actively listening animals. Here, we describe an approach to overcome these technical obstacles and address the hypothesis that a specific sub-class of auditory corticofugal neuron, the layer 6 corticothalamic neuron (L6 CT), plays an essential role in sculpting enhanced cortical and perceptual processing of expected sounds. In Aim 1, we will use cutting-edge methods for cell type-specific imaging and electrophysiology in awake, behaving mice to make targeted recordings from two classes of auditory subcerebral projection neurons: layer 5 corticocollicular neurons (L5 CCol) and L6 CTs. We expect to find stark differences in the auditory tuning, sensitivity to internal state variables, local outputs and monosynaptic inputs of L5 CCol and L6 CT neurons (Aim 1a-1d, respectively). In Aim 2, we will record from targeted subtypes of auditory cortex neurons as mice learn to form a spatiotemporal filter for processing expected sounds. We will address the hypothesis that L6 CT neurons modify their activity shortly before the onset of expected sounds to optimize cortical processing of behaviorally relevant signals. In Aim 3, we will test the causal involvement of L6 CT spike patterning for enhanced processing of expected sounds by optogenetically silencing their activity at key times in well-trained mice (to test necessity) or activating them in naïve mice (to test sufficiency). Collectively, these experiments will reveal neural circuit mechanisms that support the selection of bottom-up inputs for enhanced perceptual processing during active listening. By extension, improper regulation of this circuit could underlie the irrepressible awareness of unwanted or distracting sounds (e.g., attention deficit hyperactivity disorder) or the perception of sounds that do not exist in the environment (e.g., tinnitus and schizophrenia). 

项目摘要 在主动聆听期间，分散注意力，无关紧要或完全可预测的声音功能被抑制和 不要提高感知意识。相比之下，选择进行放大的输入传达了行为相关的 听觉信号用于指导正在进行的感知决策。神经回路机制 有选择地抑制或放大自下而上的输入以支持主动聆听仍然很神秘。 从逻辑上讲，支持主动聆听的神经元将具有来自编码的认知信号的输入 期望，注意选择和任务要求，但也能够调整收益和调整 编码或计算自下而上的声音功能的低级听觉神经元。庞大的网络 下降的听觉皮层神经元适合该钞票，因为它们的细胞体嵌入了高度塑料中 皮质声处理中心，但其轴突支配丘脑中皮层下听觉核， 中脑和脑干。解决皮质法果神经元参与主动聆听行为的参与已有 由于隔离和操纵特定类别的听觉皮层的技术困难，因此是挑战者 神经元醒着，积极地听动物。在这里，我们描述了一种克服这些技术的方法 障碍并解决了一个特定的听觉皮层神经元的属性的假设，第6层 皮质丘脑神经元（L6 CT）在雕刻增强的皮质和感知中起着至关重要的作用 预期声音的处理。在AIM 1中，我们将使用尖端的方法进行特定于细胞类型的成像和 清醒中的电生理学，表现出从两类听觉的靶向录音中的行为 脑部投影神经元：第5层皮质胶囊神经元（L5 CCOL）和L6 CTS。我们希望找到鲜明的 听觉调整的差异，对内部状态变量的敏感性，本地输出和单突触输入 L5 CCOL和L6 CT神经元（分别为AIM 1A-1D）。在AIM 2中，我们将从目标亚型中记录 听觉皮层神经元随着小鼠学习形成一个时空过滤器，用于处理预期的声音。我们将 解决了以下假设：L6 CT神经元在预期声音发作之前不久将其活性修改为 优化行为相关信号的皮质处理。在AIM 3中，我们将测试L6的因果关系 CT尖峰图案构图，以增强预期声音的处理，从而使他们的活性沉默 训练有素的小鼠的关键时间（以测试必要的小鼠）或在幼稚的小鼠中激活它们（以测试足够）。 总的来说，这些实验将揭示支持自下而上的神经回路机制 在主动聆听过程中，用于增强感知处理的输入。通过扩展，对此的不当调节 电路可能是对不需要或分散注意力的不可抑制的意识的基础（例如，注意力不足 多动症）或环境中不存在的声音的感知（例如耳鸣和 精神分裂症）。