Integration of ascending and descending input to auditory cortex

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集成增强了我们 识别嘈杂环境中的刺激，并加快感应器和运动器的集成。中国的赤字 这种能力在自闭症、精神分裂症和注意力集中等神经病理中很常见。 缺乏性多动障碍。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觉信息的调制是至关重要的， 但人们对其中涉及的神经机制知之甚少。这件事的重要性 意识的过程是通过麻醉剂诱导的选择性丧失而提出的 催眠和慢波睡眠时。在这里，我们建议研究细胞和 听皮层这一整合过程的电路机制及其调节 全身麻醉剂。 基于对上行和下行传入到 柱状细胞和具有明显树突状树枝的细胞类型，我们建议整合 升序和降序输入的大小将因细胞类型而异。层流位置和 上升和下降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 对于任何皮质区域，包括听觉皮质，都知之甚少。我们预测 下行输入将改变由上行引起的时空活动模式 这一过程的动力学将取决于突触 上行和下行传入的生理学和局部神经的接触 抑制性过程。我们将使用钙成像、电生理学和解剖学在 用初级听觉皮质(A1)的脑片来验证这些假设。三个具体的 目标将得到解决。我们将研究上升和下降的整合 在层2/3和层5的锥体细胞中的输入，我们将表征 通过下行传入的时空激活模式，我们将研究 催眠药对A1上行和下行输入的影响。 了解皮质电路如何整合来自外部和内部的信息 SOURCES是理解感觉加工和神经基础的基础 感官意识，具有重要的临床意义和实用价值。传统型 只关注自下而上处理和最高层融合的观点 大脑皮层层次结构的水平受到自上而下影响的研究的挑战 并强调了初级感觉区域对 知觉现象。了解麻醉剂所致损失的皮质机制 将有助于对含有较少催眠药物的设计的研究 对血液动力学和中枢神经系统以外的其他现象的不良影响，并将 此外，还提供对感官知觉的神经基础的洞察。

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.