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). 

项目概要 在主动聆听过程中，分散注意力、不相关或完全可预测的声音特征会被抑制并被消除。 相比之下，选择用于放大的输入传达了行为相关的信息。 用于指导持续感知决策的听觉信号的神经回路机制。 有选择地抑制或放大自下而上的输入以支持主动倾听仍然很神秘。 从逻辑上讲，支持主动倾听的神经元将获得来自编码认知信号的输入 期望、注意力选择和任务要求，但也能够调整增益和调整 编码或计算自下而上的声音特征的低级听觉神经元。 下降的听觉皮质神经元符合要求，因为它们的细胞体嵌入高度可塑性中 皮质声音处理中心，但它们的轴突支配丘脑的皮质下听觉核， 解决中脑和脑干参与主动聆听行为的问题。 由于隔离和操纵特定类别的听觉皮层的技术难度，一直具有挑战性 在这里，我们描述了一种克服这些技术问题的方法。 障碍并解决了听觉皮质神经元的特定子类（第 6 层）的假设 皮质丘脑神经元 (L6 CT) 在塑造增强的皮质和知觉方面发挥着重要作用 在目标 1 中，我们将使用尖端方法进行细胞类型特异性成像和处理。 电生理学对清醒、行为正常的小鼠进行两类听觉的有针对性的记录 脑下投射神经元：第 5 层皮质神经元 (L5 CCol) 和 L6 CT。 听觉调谐、对内部状态变量的敏感性、局部输出和单突触输入的差异 L5 CCol 和 L6 CT 神经元（分别为目标 1a-1d）。在目标 2 中，我们将从目标亚型进行记录。 当小鼠学会形成时空过滤器来处理预期的声音时，听觉皮层神经元我们会。 解决了 L6 CT 神经元在预期声音出现前不久改变其活动的假设 优化行为相关信号的皮层处理 在目标 3 中，我们将测试 L6 的因果参与。 CT 尖峰图案通过光遗传学方式抑制预期声音的活动来增强对预期声音的处理 在训练有素的小鼠中激活关键时间（以测试必要性）或在未经训练的小鼠中激活它们（以测试充分性）。 总的来说，这些实验将揭示支持自下而上选择的神经回路机制 主动聆听期间增强感知处理的输入，进而导致对此的不当调节。 电路可能是对不想要的或分散注意力的声音的不可抑制的意识的基础（例如，注意力缺陷 多动症）或对环境中不存在的声音的感知（例如耳鸣和 精神分裂症）。