GABAergic Circuits in Auditory Cortex

描述（由申请人提供）：我们的长期目标是了解皮质GABAA受体介导的抑制在感觉刺激知觉中的作用，以及全身麻醉剂对GABAA受体的调节和各种神经病变中皮质抑制的变化如何改变感觉知觉。在本研究中，我们试图了解gaba能细胞如何控制听觉皮层（ACx）动作电位的时间。分布在ACx锥体细胞群中的放电模式被认为代表了声刺激的某些特征。这些人口编码中的峰值要么是时间锁定的，要么是由内部产生的时间模式组成的。有证据表明，皮层中间神经元网络参与了这两种模式的建立。丘脑皮质（TC）事件激活ACx中多个“前馈”gaba能中间神经元群。门神经TC纤维作用于III层和IV层细胞（LIII/IV），而门神经外TC传入作用于I层细胞（LI）。后一种事件的激活触发ACx的伽马频率振荡。我们提出ACx中的前馈中间神经元调节锥体细胞的尖峰时间，并且这种能力通过抑制细胞之间的网络相互作用而增强。我们将验证LI中间神经元控制内部产生的放电模式的假设，而LIII/IV中间神经元协调时间锁定刺激的放电模式。皮质定时信号的中断也被认为是全身麻醉期间感觉和认知障碍的基础，并且ACx中皮质节律的调节正在被寻求作为监测患者麻醉深度的重要医学应用的解决方案。gaba能中间神经元在正常、病理和外源性调节的皮层加工过程中起着中心作用。因此，了解这些细胞是如何被激活和组织的，以及这种结构的功能含义对于理解皮层信息处理至关重要。尽管有大量证据表明这些细胞在设定主细胞的反应特性方面起着关键作用，但我们试图填补我们对它们的组织以及它们如何与主细胞相互作用的知识空白。

DESCRIPTION (provided by applicant): Our long-term objective is to understand the role of cortical GABAA receptor-mediated inhibition in the perception of sensory stimuli, and how modulation of GABAA receptors by general anesthetics and changes in cortical inhibition in various neuropathologies alters sensory perception. In this proposal, we seek to understand how GABAergic cells control the timing of action potentials in auditory cortex (ACx). Firing patterns distributed across populations of pyramidal cells in ACx are postulated to represent certain features of acoustic stimuli. Spikes in these population codes are either time-locked to transitions in the stimulus, or comprise temporal patterns generated internally. Evidence suggests that networks of cortical interneurons are involved in establishing both types of patterns. Thalamocortical (TC) afferents activate multiple populations of 'feedforward' GABAergic interneurons in ACx. Lemniscal TC fibers target cells in layers III and IV (LIII/IV), while extralemniscal TC afferents target cells in layer I (LI). Activation of the latter afferents triggers gamma frequency oscillations in ACx. We propose that feedforward interneurons in ACx regulate spike timing in pyramidal cells and that this capability is enhanced by network interactions among inhibitory cells. We will test the hypothesis that LI interneurons control internally generated firing patterns, while LIII/IV interneurons coordinate firing patterns that are time-locked to the stimulus. Disruption of cortical timing signals has also been postulated to underlie sensory and cognitive impairment during general anesthesia, and modulation of cortical rhythms in ACx is being pursued as a solution to the important medical application of monitoring depth of anesthesia in patients. GABAergic interneurons are central players in normal, pathological and exogenously modulated cortical processing. Thus, understanding how these cells are activated and organized and the functional implications of this structure is critical to understanding cortical information processing. Although evidence abounds that these cells play a pivotal role in setting the response properties of principal cells, we seek to fill the gap in our knowledge of their organization and how they interact with principal cells.