GABAergic Circuits in Auditory Cortex

听觉皮层中的 GABA 能回路

• 批准号: 7342867
• 负责人: Matthew I Banks
• 金额: $ 22.6万
• 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 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7342867
• 关键词: Acoustics; Action Potentials; Anatomy; Anesthesia procedures; Area; Auditory area; Brain; Cells; Chemicals; Code; Computer Simulation; Computer information processing; Coupling; Data; Depth; Disruption; Electrical Synapse; Fiber; Fire - disasters; Frequencies; General Anesthesia; General anesthetic drugs; Generations; Impaired cognition; Incidence; Interneurons; Kinetics; Knowledge; Label; Maps; Measures; Mediating; Medical; Membrane Potentials; Monitor; Morphology; Mus; Patients; Pattern; Perception; Physiological; Physiology; Play; Population; Probability; Process; Property; Pyramidal Cells; Regulation; Role; Sensory; Signal Transduction; Simulate; Slice; Solutions; Stimulus; Structure; Synapses; Techniques; Testing; Thalamic structure; Time; Whole-Cell Recordings; base; neuropathology; patch clamp; receptor; response; sensory stimulus; simulation

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.

我们的长期目标是了解皮质GABAA受体介导的抑制在 感官刺激的感知，以及如何通过全身麻醉和 各种神经病理学中皮质抑制的变化改变了感觉知觉。在这个建议中，我们 寻求了解GABA能细胞如何控制听觉皮层（ACX）中作用电位的时机。 假设在ACX中分布在锥体细胞种群中 声刺激的某些特征。这些人口代码中的尖峰要么滞留到过渡 在刺激中，或包含内部产生的时间模式。有证据表明网络 皮质中间神经元参与建立两种类型的模式。丘脑皮质（TC）传入 激活ACX中“进食” GABA能中间神经元的多个种群。 Lemniscal TC纤维靶标 层III和IV（LIII/IV）中的细胞，而验证的TC传入量I（LI）中的细胞靶向细胞。激活 后者传入触发ACX中的伽马频率振荡。我们提出了那个饲料 ACX中的元素调节锥体细胞中的尖峰计时，并且这种能力通过 抑制细胞之间的网络相互作用。我们将检验以下假设：李中间神经元控制 内部生成的射击模式，而LIII/IV中间神经元协调触发模式为 时间锁定到刺激上。皮质计时信号的破坏也被假定为基础 全身麻醉期间的感觉和认知障碍，以及ACX中皮质节律的调节 正在为监测麻醉深度的重要医学应用而追求 患者。 GABA能中间神经元是正常，病理和外源的中心参与者 调节皮质加工。因此，了解这些细胞是如何被激活和组织的， 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置响应特性中起关键作用 ）rincipal细胞，我们试图填补我们对组织的了解以及他们如何互动的空白 ）凹形细胞。