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， 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， 在嘈杂的环境中识别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集中症等神经病中很常见 缺陷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对输入的感觉信息的调节是至关重要的， 但对其中的神经机制知之甚少。这一点的重要性 意识的过程是由其在麻醉诱导的选择性丧失所暗示的。 催眠和慢波睡眠。在这里，我们建议调查细胞和 这一整合过程在听觉皮层的电路机制及其调制 全身麻醉药 基于对一个上行和下行传入的层流分离， 柱和具有不同树突状分支的细胞类型，我们建议整合 的升序和降序输入将是特定于细胞类型的。椎板位置和 由上行和下行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， 对任何皮层区域都知之甚少，包括听觉皮层。我们预测 下行输入将改变上行输入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 上行和下行传入的生理学和局部 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）的大脑切片来验证这些假设。三个具体 目标将得到解决。我们将研究上升和下降的整合 通过2/3层和5层锥体细胞中的输入，我们将描述 下行传入的时空激活模式，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的信息 来源是理解感觉处理的神经基础的基础， 感官意识，并具有重要和实际的临床意义。传统 只注重自下而上的处理和最高层的融合的观点 大脑皮层等级的水平受到了研究的挑战，研究表明， 层次结构的所有级别，并强调初级感觉区域的重要性， 知觉现象了解麻醉诱导损失的皮质机制 将有利于研究催眠药物的设计， 对血液动力学和CNS外的其他现象产生不良影响， 此外，它还提供了对感官意识的神经基础的洞察。

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.