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）：感官知觉是由先前的经验和期望形成的，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，并加快了感觉运动整合。这种能力的缺陷在自闭症、精神分裂症和注意缺陷多动障碍等神经病理学中很常见。有证据表明，大脑皮层中的反馈回路对于这种对传入感觉信息的经验依赖性调制至关重要，但所涉及的神经机制却知之甚少。麻醉诱导的催眠和慢波睡眠期间，这一过程的选择性丧失表明了这一过程对意识的重要性。在这里，我们建议调查的细胞和电路机制，这一整合过程中的听觉皮层和全身麻醉药的调制。基于层流隔离的上行和下行传入的列和细胞类型与不同的树突状分支，我们建议，整合的上行和下行输入将是细胞类型特异性的。由上行和下行输入激活的细胞的层位置和时间序列，以及这些输入的突触生理学，对于理解柱状整合至关重要，但对于任何皮层区域（包括听觉皮层）都知之甚少。我们预测，下降的输入将改变上升的输入列引起的时空活动模式，这个过程的动态将取决于上升和下降的传入和参与当地的抑制过程的突触生理。我们将使用钙成像，电生理学和解剖学在大脑切片的初级听觉皮层（A1）来测试这些假设。将讨论三个具体目标。我们将研究在锥体细胞的第2/3层和第5层的上行和下行输入的整合，我们将表征下行传入的时空激活模式的调制，我们将研究催眠药物对A1的上行和下行输入的影响。了解皮层回路如何整合来自外部和内部来源的信息是理解感觉处理和感觉意识的神经基础的基础，并具有重要和实际的临床意义。传统的观点认为，自下而上的处理和聚合只在最高层次的皮层层次的挑战研究显示，自上而下的影响，在所有层次的层次，并强调了知觉现象的主要感觉区域的重要性。了解麻醉诱导的意识丧失的皮质机制将有助于设计对血液动力学和CNS外其他现象具有较少不良影响的催眠药物的研究，并且还将提供对感觉意识的神经基础的深入了解。感知是由先前的经验和期望塑造的，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，并加快了感觉运动整合。这种能力的缺陷在自闭症、精神分裂症和注意缺陷多动障碍等神经病理学中很常见。有证据表明，大脑皮层中的反馈回路对于这种对传入感觉信息的经验依赖性调制至关重要，但所涉及的神经机制知之甚少。拟议的实验将阐明这样一个皮层反馈回路如何影响传入的听觉信息的处理。