Integration of ascending and descending input to auditory cortex

整合听觉皮层的上升和下降输入

• 批准号: 7893247
• 负责人: Matthew I Banks
• 金额: $ 30.62万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-03-15 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7893247
• 关键词: Address; Affect; Afferent Pathways; Anatomy; Anesthetics; Area; Attention deficit hyperactivity disorder; Auditory; Auditory area; Autistic Disorder; Awareness; Behavioral; Biological Assay; Brain; Calcium; Cells; Cerebral cortex; Clinical; Cortical Column; Data; Dendritic Cells; Depressed mood; Dose; Electrophysiology (science); Environment; Exhibits; Feedback; Fire - disasters; Fluorescence; General anesthetic drugs; Hypnosis; Image; Imaging Techniques; Left; Link; Measures; Modality; Modeling; Monitor; Neocortex; Pattern; Perception; Pharmaceutical Preparations; Physiology; Positioning Attribute; Preparation; Process; Pyramidal Cells; Regulation; Relative (related person); Research; Resolution; Schizophrenia; Sensory; Sensory Process; Shapes; Signal Transduction; Slice; Slow-Wave Sleep; Source; Speed; Stimulus; Stream; Synapses; Techniques; Testing; Thalamic structure; Time; Unconscious State; Visual Cortex; Whole-Cell Recordings; base; cell type; clinically relevant; density; design; expectation; experience; hemodynamics; hypnotic; in vivo; insight; neuromechanism; neuropathology; patch clamp; receptive field; relating to nervous system; research study; response; segregation; sensory cortex; sensory stimulus; spatiotemporal; tool; white matter

DESCRIPTION (provided by applicant): Sensory perceptions are shaped by prior experience and expectation, and integration of these top-down and bottom-up information streams enhances our ability to identify stimuli in noisy environments and speeds sensorimotor integration. Deficits in this ability are common in neuropathologies such as autism, schizophrenia and attention deficit hyperactivity disorder. Evidence suggests that feedback circuits in cerebral cortex are critical for this experience-dependent modulation of incoming sensory information, but the neural mechanisms involved are poorly understood. The importance of this process for awareness is suggested by its selective loss upon anesthetic-induced hypnosis and during slow-wave sleep. Here, we propose to investigate the cellular and circuit mechanisms of this integrative process in auditory cortex and its modulation by general anesthetics. Based on the laminar segregation of ascending and descending afferents to a column and of cell types with distinct dendritic arborization, we suggest that integration of ascending and descending inputs will be cell-type specific. The laminar position and temporal sequence of cells activated by ascending and descending inputs, as well as these inputs' synaptic physiology, are critical to understanding columnar integration, but are poorly understood for any cortical area, including auditory cortex. We predict that descending inputs will alter the spatiotemporal activity pattern induced by ascending inputs to the column, and that the dynamics of this process will depend on the synaptic physiology of ascending and descending afferents and the engagement of local inhibitory processes. We will use calcium imaging, electrophysiology, and anatomy in brain slices of primary auditory cortex (A1) to test these hypotheses. Three specific aims will be addressed. We will investigate the integration of ascending and descending inputs in pyramidal cells of layer 2/3 and layer 5, we will characterize the modulation of spatiotemporal activation patterns by descending afferents, and we will investigate the effects of hypnotic agents on ascending and descending inputs to A1. Understanding how cortical circuits integrate information from external and internal sources is fundamental to understanding the neural basis of sensory processing and sensory awareness, and has important and practical clinical implications. Traditional views that have focused on bottom-up processing and convergence only at the highest levels of the cortical hierarchy are challenged by studies showing top-down influences at all levels of the hierarchy and highlighting the importance of primary sensory regions for perceptual phenomena. Understanding cortical mechanisms of anesthetic-induced loss of consciousness will benefit research into the design of hypnotic drugs that have fewer undesirable effects on hemodynamics and other phenomena outside the CNS, and will additionally provide insight into the neural basis of sensory awareness. Perceptions are shaped by prior experience and expectation, and integration of these top-down and bottom-up information streams enhances our ability to identify stimuli in noisy environments and speeds sensorimotor integration. Deficits in this ability are common in neuropathologies such as autism, schizophrenia and attention deficit hyperactivity disorder. Evidence suggests that feedback circuits in cerebral cortex are critical for this experience- dependent modulation of incoming sensory information, but the neural mechanisms involved are poorly understood. The proposed experiments will elucidate how one such cortical feedback circuit affects the processing of incoming auditory information.

描述（由申请人提供）：感官感知是由先前的经验和期望来塑造的，这些自上而下和自下而上的信息流的整合增强了我们在嘈杂环境中识别刺激的能力，并加快了感觉运动集成的速度。这种能力的缺陷在自闭症，精神分裂症和注意力缺陷多动障碍等神经病理学中很常见。有证据表明，脑皮质中的反馈电路对于这种依赖于传入的感觉信息的经验调节至关重要，但是所涉及的神经机制知之甚少。该过程对意识的重要性是由于其在麻醉引起的催眠和慢波睡眠期间的选择性损失所表明的。在这里，我们建议研究听觉皮层中这种整合过程的细胞和电路机制及其通过一般麻醉的调节。基于对具有独特的树突状树皮化的列的升和下降传入的层次分离，我们建议将上升和降序输入的整合是特定于细胞类型的。通过上升和下降输入激活的细胞的层状位置和时间序列以及这些输入的突触生理学对于理解柱状整合至关重要，但对于包括听觉皮层在内的任何皮质区域，对柱状的整合都很了解。我们预测，下降输入将改变通过上升到列的升级输入引起的时空活动模式，并且该过程的动力学将取决于上升和下降传入的突触生理以及局部抑制过程的参与。我们将在原发性听觉皮层（A1）的脑切片中使用钙成像，电生理学和解剖结构来检验这些假设。将解决三个具体目标。我们将研究第2/3和第5层的锥体细胞中上升和下降输入的整合，我们将通过降低传入来表征时空激活模式的调节，我们将研究催眠药物对升序和下降输入对A1的影响。了解皮层电路如何整合来自外部和内部来源的信息对于理解感觉处理和感觉意识的神经基础是至关重要的，并且具有重要且实际的临床意义。仅在皮质层次结构最高水平的自下而上处理和收敛的传统观点受到研究的挑战，即在层次结构的各个层面上的自上而下影响，并突出了主要感觉区域对感知现象的重要性。了解麻醉性引起的意识丧失的皮质机制将使对催眠药的设计有益于对血液动力学和中枢神经系统外的其他现象的不良影响的设计，并将提供对感官意识的神经基础的见解。感知是由先前的经验和期望来塑造的，这些自上而下和自下而上的信息流的整合增强了我们在嘈杂的环境中识别刺激的能力，并加快了感觉运动集成的速度。这种能力的缺陷在自闭症，精神分裂症和注意力缺陷多动障碍等神经病理学中很常见。有证据表明，大脑皮层中的反馈电路对于这种依赖于传入的感觉信息的经验调节至关重要，但是所涉及的神经机制的理解很少。提出的实验将阐明一个这样的皮质反馈电路如何影响传入听觉信息的处理。