Cellular Physiology of Neuronal Circuits in Neocortex

新皮质神经元回路的细胞生理学

• 批准号: 7204166
• 负责人: Barry W Connors
• 金额: $ 34.13万
• 依托单位: BROWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7204166
• 关键词: Anxiety; Axon; Behavior; Brain region; Cell Nucleus; Cell physiology; Cells; Cerebral cortex; Chromosome Pairing; Cognition; Cognitive; Complex; Dependence; Disease; Epilepsy; Esthesia; Feedback; Goals; Human; In Vitro; Interneurons; Measures; Mediating; Mediator of activation protein; Mental disorders; Methods; Molecular; Motor; Movement; Mus; Neocortex; Network-based; Neurologic; Neuromodulator; Neurons; Output; Pathway interactions; Physiological; Play; Process; Property; Proteins; Pyramidal Cells; Research Personnel; Role; Schizophrenia; Seizures; Slice; Source; Spatial Distribution; Staging; Synapses; Synaptic Membranes; System; Testing; Thalamic structure; Time Study; Transgenic Mice; Transgenic Organisms; Work; cell type; inhibitory neuron; insight; interest; neocortical; novel; postsynaptic; presynaptic; programs; research study; response; sensory mechanism; somatosensory; spatiotemporal; tool; voltage

DESCRIPTION (provided by applicant): The thalamus and neocortex are 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 interneurons and their roles in the earliest stages of thalamocortical processing; 2) To characterize the roles of these interneurons 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 record from identified interneurons, 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.

描述（由申请人提供）：丘脑和新皮层对于正常的感觉、运动和认知是必不可少的，它们以亲密的、不可分割的联系起作用。丘脑是几乎所有进入新皮层的特定信息的来源，而新皮层反过来又向丘脑发送大量反馈。丘脑和新皮层中的特定抑制性神经元是通过丘脑皮层系统的信息流的关键调节器。我的建议的中心目标是了解这些抑制性神经元及其突触的各种功能。有四个具体目标：1）描述两种不同类型的新皮层抑制性中间神经元及其在丘脑皮层加工的早期阶段的作用; 2）描述这些中间神经元在新皮层局部回路中的作用; 3）测试抑制功能的活性依赖性和状态依赖性; 4）描述丘脑网状核的突触连接。我们将使用转基因小鼠来识别和选择感兴趣的神经元，各种体外方法来记录已识别的中间神经元，解剖学方法来验证和表征神经元类型，以及药理学和分子工具来操纵细胞和突触。拟议的实验将提供新的和重要的洞察丘脑皮质系统的细胞抑制机制。这些信息对于我们理解感觉、运动和认知过程及其障碍的机制至关重要。描述：大脑皮层和它的伙伴，丘脑，是最复杂和独特的人类行为的关键大脑区域。皮质和丘脑中抑制性神经细胞的缺失与癫痫、精神分裂症、焦虑和其他神经和精神疾病有关。这里提出的实验将描述抑制细胞的正常功能，以便更合理地评估它们在疾病中的作用。