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Excitation and Inhibition Balance: Sensitive Period Plasticity

兴奋与抑制平衡：敏感期可塑性

基本信息

批准号：
8574483
负责人：
Qian-Quan Sun
金额：
$ 42.11万
依托单位：
UNIVERSITY OF WYOMING
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-08-01 至 2017-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8574483
关键词：
Adult Autistic Disorder Axon Behavioral Brain Cerebral cortex Characteristics Child Cognitive Data Development Diagnosis Disease Education Emotional Epilepsy Equilibrium Functional disorder Genetic Goals Health Human Individual Interneurons Knowledge Life Maintenance Mediating Mus Nature Neocortex Neurons Neurosciences Research Pathway interactions Population Probability Process Property Regulation Research Rhodopsin Rodent Role Schizophrenia Sensory Sensory Deprivation Sensory Neglects Shapes Signal Transduction Staging Students Synapses System Testing United States Universities Vibrissae Work Wyoming barrel cortex career child neglect developmental disease environmental enrichment for laboratory animals experience graduate student in vivo innovation innovative technologies interest neglect nervous system disorder neuron development novel postnatal public health relevance social stellate cell undergraduate student

项目摘要

DESCRIPTION (provided by applicant): During early postnatal brain development, neurons in the cerebral cortex establish connections that are then fine-tuned by experience-dependent mechanisms. Disturbances in the balance of excitation (E) and inhibition (I) in the neocortex provoke abnormal activities, such as epileptic seizures and abnormal cortical development. Mechanisms that match E-I balance are central to achieving balanced function at the level of individual neuron and circuits. However, the precise nature of E-I balance, and specific mechanisms orchestrating the establishment and maintenance of the E-I balance in adult cortical neurons is largely unknown. Circuit-wide studies documenting coordinated changes in E and I within a functional circuit are rare. Our long-term goal is to use rodent whisker-barrel system to understand the mechanisms by which the developing inhibitory networks in barrel cortex are able to adapt to sensory inputs from whiskers, and to maintain their balance with cortical excitatory networks. Applying innovative mouse genetics and channel rhodopsin assisted circuit targeting, the present proposal will investigate whether a specific, defined interaction between sensory activities with excitatory (E) and inhibitory (I) synapses may be involved in regulating E-I balance during the sensitive period of postnatal development. A major advance in this proposal is to provide new information regarding pathway and input specific E/I balance and their differential modulation by sensory experiences. Because network processing in vivo is driven by specific inputs, understanding input specific regulation of the E-I balance an its maturation is significant. If successful, this proposal will generate novel data and hypotheses for understanding of the roles of sensory experiences in shaping cortical synaptic connectivity at early stages of life. The impact of restricting neuronal activity through sensory neglect is eviden in the human population. Each year in the United States alone, over 500,000 children suffer from "neglect" and have a much higher probability of emotional, behavioral, cognitive, and physical delays than average children. As such, research aimed at identifying mechanisms underlying activity-induced plasticity of brain circuits and brain function also has significant health relevance. This research will obtain baseline knowledge about normal cortex function, which is critically needed to understand cortical processing deficits in disease states. Thus, this research will potentially advance and expand understanding, diagnosis, and treatment of human developmental disorders with a deregulated E-I balance. The proposed research will have substantial effect on the neuroscience research and education at the University of Wyoming. Engaging students in this innovative research will instigate their interest in pursuing career innovative research.

描述（由申请人提供）：在出生后早期的大脑发育过程中，大脑皮层中的神经元建立连接，然后通过经验依赖机制进行微调。新皮层中兴奋（E）和抑制（I）平衡的紊乱引起异常活动，如癫痫发作和异常皮层发育。匹配E-I平衡的机制是在单个神经元和回路水平上实现平衡功能的核心。然而，E-I平衡的确切性质，以及在成年皮层神经元中建立和维持E-I平衡的具体机制在很大程度上是未知的。记录功能回路内E和I协调变化的全回路研究很少。我们的长期目标是利用啮齿动物的胡须-桶系统来了解桶皮层中发育中的抑制网络能够适应来自胡须的感觉输入并维持它们与皮层兴奋网络的平衡的机制。应用创新的小鼠遗传学和通道视紫红质辅助电路靶向，本提案将调查是否有一个特定的，定义的兴奋性（E）和抑制性（I）突触的感觉活动之间的相互作用可能参与调节E-I平衡在出生后发育的敏感期。这一建议的一个主要进展是提供新的信息，途径和输入特定的E/I平衡和它们的差异调制的感觉经验。由于体内的网络处理是由特定的输入驱动的，因此理解E-I平衡及其成熟的输入特异性调节是重要的。如果成功的话，这一提议将产生新的数据和假设。以了解感官体验在生命早期形成皮层突触连接中的作用。通过感觉忽视限制神经元活动的影响在人群中是明显的。仅在美国，每年就有超过50万名儿童遭受“忽视”，他们在情感、行为、认知和身体方面的延迟比普通儿童要高得多。因此，旨在确定活动诱导的脑回路和脑功能可塑性的潜在机制的研究也具有重要的健康相关性。这项研究将获得关于正常皮层功能的基线知识，这是理解疾病状态下皮层处理缺陷所急需的。因此，研究将潜在地推进和扩展对E-I平衡失调的人类发育障碍的理解、诊断和治疗。该研究将对怀俄明州大学的神经科学研究和教育产生重大影响。让学生参与这项创新研究将激发他们追求职业创新研究的兴趣。