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层GABAA受体介导的抑制在脑缺血中的作用。 感觉刺激的感知，以及全身麻醉剂和 在各种神经病理学中皮质抑制的变化改变感觉知觉。在本提案中，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假定代表 声音刺激的某些特征。这些种群代码中的尖峰要么时间锁定到转换 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 III层和IV层（LIII/IV）的细胞，而外丘系TC传入的靶细胞在I层（LI）。激活 后者传入触发ACx中的伽马频率振荡。我们建议前馈 ACx中的中间神经元调节锥体细胞中的发放时间，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L1中间神经元控制 内部产生的放电模式，而LIII/IV中间神经元协调放电模式， 时间锁定在刺激上皮质定时信号的中断也被认为是 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 作为监测麻醉深度的重要医学应用的解决方案， 患者GABA能中间神经元是正常、病理和外源性神经元损伤的中枢参与者。 调制皮层处理因此，了解这些细胞是如何被激活和组织的， 这种结构的功能意义对于理解皮层信息处理至关重要。 尽管有大量证据表明，这些细胞在设定细胞的反应特性中起着关键作用， ）在UNRcell中，我们试图填补我们对其组织及其如何与 ）rinUNR细胞。