Cellular Physiology of Neuronal Circuits in Neocortex

摘要：丘脑和新皮质对于正常的感觉、运动和认知是必不可少的。 他们以亲密、密不可分的关系工作。丘脑几乎是所有特定信息的来源 进入新大脑皮层，新大脑皮层又向丘脑发送大量反馈。特定的 丘脑和新皮质中的抑制性神经元是信息流动的关键调节者。 丘脑皮质系统。我的建议的中心目标是了解一些 这些抑制性神经元和它们的突触。有四个特定的目的：1)表征两个明显的 不同类型的新皮质抑制性中间神经元及其在丘脑皮质早期的作用 加工；2)表征这些中间神经元在大脑皮层局部环路中的作用；3)测试 抑制功能的活性和状态依赖性；4)表征突触与突触之间的联系 在丘脑网状核内。我们将使用转基因小鼠品系来鉴定和选择神经元 有趣的是，各种体外方法记录来自已鉴定的中间神经元，解剖学方法来验证 并描述神经元类型，以及操纵细胞和突触的药理学和分子工具。 拟议中的实验将为抑制的细胞机制提供新的和重要的见解 在丘脑皮质系统中。这些信息将对我们理解 感觉、运动和认知加工的机制及其紊乱。 描述：大脑皮层及其伙伴丘脑是大脑中最复杂的区域 和独特的人类行为。大脑皮质和丘脑中抑制性神经细胞的异常 与癫痫、精神分裂症、焦虑症以及其他神经和精神疾病有关。这个 这里提出的实验将描述抑制细胞的正常功能，以便它们在 可以更合理地评估疾病。

Abstract: The thalamus and neocortexare essential for normal sensation, movement, and cognition, and they work in intimate, inextricable association. The thalamus is the origin of virtually all specific information entering the neocortex, and the neocortex in turn sends massive feedback to the thalamus. Specific inhibitory neurons in both the thalamus and neocortex are critical regulators of information flow through the thalamocortical system. The central goal of my proposal is to understand the diverse functions of some of these inhibitory neurons and their synapses.There are four specific aims: 1) To characterize two distinctly different types of neocortical inhibitory intemeurons and their roles in the earliest stages of thalamocortical processing; 2) To characterize the roles of these intemeurons in local circuits in the neocortex; 3) To test the activity- and state-dependence of inhibitory functions; 4) To characterize synaptic connections to, from, and within the thalamic reticular nucleus. We will use transgenic lines of mice to identify and select the neurons of interest, a variety of in vitro methods to recordfrom identified intemeurons, anatomical methods to verify and characterize neuron types, and pharmacological and molecular tools to manipulate cells and synapses. The proposed experiments will provide novel and important insight into the cellular mechanisms of inhibition in the thalamocortical system. This information will be of central importance to our understanding of the mechanisms of sensory, motor, and cognitive processing and their disorders. Description: The cerebral cortex and its partner, the thalamus, are brain regions critical for the most complex and uniquely human behaviors. Abnormalities of inhibitory nerve cells in the cortex and thalamus have been implicated in epilepsy, schizophrenia, anxiety, and other neurological and psychiatric diseases. The experiments proposed here will characterize the normal functions of inhibitory cells, so that their roles in disease can be more rationally evaluated.