GABAergic Circuits in Auditory Cortex

听觉皮层中的 GABA 能回路

• 批准号: 6605959
• 负责人: Matthew I Banks
• 金额: $ 27.96万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-03-15 至 2008-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6605959
• 关键词: GABA receptor; action potentials; auditory cortex; auditory stimulus; gamma aminobutyrate; interneurons; laboratory mouse; neural transmission; pyramidal cells; sensory deprivation; tissue /cell culture; voltage /patch clamp

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.

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知刺激感知中的作用，以及一般麻醉剂对GABAA受体的调节以及在各种神经病理学中的皮质抑制作用的变化如何改变感觉感知。在此提案中，我们试图了解GABA能细胞如何控制听觉皮层（ACX）中动作电位的时机。假定在ACX中分布在锥体细胞种群中的发射模式，以表示声刺激的某些特征。这些种群代码中的尖峰要么锁定在刺激中的过渡中，要么包含内部产生的时间模式。证据表明，皮质中间神经元网络参与建立两种类型的模式。丘脑皮层（TC）传入激活了ACX中“进食” GABA能中间神经元的多个种群。 Lemniscal TC纤维靶向III和IV层（LIII/IV）中的细胞，而验证的TC传入量I（LI）中的细胞靶向细胞。后一种传入的激活会触发ACX中的伽马频率振荡。我们提出，ACX中的前馈中神经元调节锥体细胞中的尖峰时序，并且通过抑制细胞之间的网络相互作用增强了这种能力。我们将检验以下假设：LI中间神经元控制内部产生的射击模式，而LIII/IV中间神经元协调了滞留在刺激上的发射模式。皮质计时信号的破坏也被认为是全身麻醉期间的感觉和认知障碍的基础，并且正在追求ACX中皮质节律的调节，以解决患者麻醉深度的重要医学应用。 GABA能中间神经元是正常，病理和外源调节的皮质加工的中心参与者。因此，了解这些细胞是如何被激活和组织的，并且该结构的功能含义对于理解皮质信息处理至关重要。尽管有证据表明这些细胞在设定主要细胞的响应特性中起着关键作用，但我们试图填补我们对组织的知识以及它们如何与主细胞相互作用的空白。