GABAergic Circuits in Auditory Cortex

我们的长期目标是了解皮质GABAA受体介导的抑制在 感觉刺激的知觉，以及全麻药和麻醉剂对GABA受体的调节 在各种神经病理中，皮质抑制的改变改变了感官知觉。在这项提案中，我们 试图了解GABA能细胞如何控制听觉皮质(ACX)动作电位的时序。 分布在ACX锥体细胞种群中的放电模式被假设为代表 声学刺激的某些特征。这些种群代码中的峰值要么被时间锁定到转换 在刺激中，或者包括内部产生的时间模式。有证据表明， 皮质中间神经元参与了这两种类型的模式的建立。丘脑皮质(TC)传入 激活ACX内多个“前馈”GABA能中间神经元。Lemniscal TC纤维靶标 III和IV层(LIII/IV)中的细胞，而丘脑外TC传入I层(LI)中的靶细胞。激活 后者的传入在ACX中触发伽马频率振荡。我们建议前馈 ACX中的中间神经元调节锥体细胞的棘波计时，这种能力通过 抑制细胞之间的网络相互作用。我们将检验LI中间神经元控制的假设 内部产生的放电模式，而LIII/IV中间神经元协调的放电模式 时间锁定在刺激计划上。大脑皮层计时信号的中断也被认为是 全麻期间的感觉和认知损害以及ACX对皮质节律的调节 作为监测麻醉深度的重要医学应用的一种解决方案 病人。GABA能中间神经元是正常、病理和外源性的中心角色 调制的皮质处理。因此，了解这些细胞是如何激活和组织的 这种结构的功能暗示对于理解大脑皮层信息处理至关重要。 尽管有大量证据表明，这些细胞在设定反应特性方面发挥了关键作用 )，我们试图填补我们对它们的组织以及它们如何相互作用的知识空白 )枕叶细胞。

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 intemeurons 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 )rincipal cells, we seek to fill the gap in our knowledge of their organization and how they interact with )rincipal cells.