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: 8298243
• 负责人: Matthew I Banks
• 金额: $ 30.12万
• 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/8298243
• 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

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.

感官知觉是由先前的经验和期望塑造的，并且 这些自上而下和自下而上的信息流的整合增强了我们的能力 识别嘈杂环境中的刺激并加速感觉运动整合。赤字 这种能力在自闭症、精神分裂症和注意力等神经病理学中很常见 缺乏性多动症。有证据表明大脑皮层的反馈回路 对于这种依赖于经验的传入感官信息的调制至关重要， 但人们对其中涉及的神经机制知之甚少。这一点的重要性 意识的过程是通过麻醉引起的选择性丧失来暗示的 催眠和慢波睡眠期间。在这里，我们建议研究细胞和 听觉皮层中这种整合过程的电路机制及其调节 全身麻醉剂。 基于上升和下降传入的层流分离 柱和具有不同树突分枝的细胞类型，我们建议整合 升序和降序输入的数量将是特定于细胞类型的。层流位置和 由升序和降序输入激活的细胞的时间序列，以及 这些输入的突触生理学对于理解柱状整合至关重要，但是 对包括听觉皮层在内的任何皮质区域都知之甚少。我们预测 下降的输入将改变上升引起的时空活动模式 输入到列，并且该过程的动态将取决于突触 上升和下降传入的生理学以及局部的参与 抑制过程。我们将使用钙成像、电生理学和解剖学 初级听觉皮层（A1）的脑切片来检验这些假设。三具体 将解决目标。我们将研究上升和下降的整合 输入第 2/3 层和第 5 层的锥体细胞，我们将表征 下降传入的时空激活模式，我们将研究 催眠剂对 A1 上升和下降输入的影响。 了解皮层电路如何整合外部和内部信息 来源是理解感觉处理和神经基础的基础 感官意识，具有重要而实际的临床意义。传统的 只注重自下而上的处理和最高层收敛的观点 研究表明，皮质层次结构的层次受到自上而下的影响的挑战 层次结构的所有级别，并强调主要感觉区域的重要性 知觉现象。了解麻醉引起的皮质损失机制 意识的研究将有利于催眠药物的设计研究，这些药物具有较少的 对血流动力学和中枢神经系统以外的其他现象产生不良影响，并将 此外，还提供了对感官意识的神经基础的深入了解。