GABAergic Circuits in Auditory Cortex

超出提供的空间。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知觉中的作用，以及全身麻醉剂对GABAA受体的调节和各种神经病理中皮质抑制的变化如何改变感觉感觉。在这项提议中，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锥体细胞群体中的放电模式被假设为代表声刺激的某些特征。这些群体代码中的峰值要么与刺激中的转变时间锁定，要么包括内部产生的时间模式。有证据表明，皮层中间神经元网络参与了这两种模式的建立。丘脑皮质(TC)传入激活ACX内多个“前馈”GABA能中间神经元。丘脑TC纤维以III和IV层(LIII/IV)为靶细胞，丘脑外TC纤维向I层(LI)靶细胞传入。后一种传入的激活会触发ACX中的伽马频率振荡。我们认为ACX中的前馈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而增强。我们将检验这样的假设，即LI中间神经元控制内部产生的放电模式，而LIII/IV中间神经元协调与刺激时间锁定的放电模式。在全身麻醉过程中，皮质定时信号的中断也被认为是感觉和认知损害的基础，而ACX中皮质节律的调节正在被寻求作为监测患者麻醉深度的重要医学应用的解决方案。GABA能中间神经元是正常的、病理的和外源性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，以及这种结构的功能含义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决定中枢细胞的反应特性中起着关键作用，但我们试图填补我们对其组织结构以及它们如何与中枢细胞相互作用的知识的空白。表演网站========================================Section End===========================================

EXCEED THE SPACE PROVIDED. 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. PERFORMANCE SITE ========================================Section End===========================================