GABAergic Circuits in Auditory Cortex

描述（由申请人提供）：我们的长期目标是了解皮层GABAA受体介导的抑制在感觉刺激感知中的作用，以及全身麻醉剂对GABAA受体的调节和各种神经病理学中皮层抑制的变化如何改变感觉感知。在这个提议中，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。发射模式分布在人群中的锥体细胞ACx假设代表某些功能的声刺激。这些群体代码中的尖峰要么被时间锁定到刺激中的转换，要么包括内部生成的时间模式。有证据表明，皮质中间神经元网络参与建立这两种类型的模式。丘脑皮质（TC）传入激活ACx中的多个“前馈”GABA能中间神经元群体。丘系TC纤维靶向第III层和第IV层（LIII/IV）的细胞，而丘系外TC传入靶向第I层（LI）的细胞。后者传入的激活触发ACx中的伽马频率振荡。我们建议，前馈中间神经元ACx调节尖峰时间在锥体细胞，这种能力是增强抑制性细胞之间的网络相互作用。我们将测试的假设，LI interneurons控制内部产生的放电模式，而LIII/IV interneurons协调放电模式的时间锁定的刺激。皮质定时信号的中断也被假定为全身麻醉期间感觉和认知障碍的基础，并且ACx中皮质节律的调制正被追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质加工中起着重要作用。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意义对于理解皮层信息处理至关重要。虽然有大量证据表明，这些细胞在设置主细胞的响应特性中发挥着关键作用，但我们试图填补我们对其组织以及它们如何与主细胞相互作用的知识中的差距。

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.