Excitation and Inhibition Balance: Sensitive Period Plasticity

描述（由申请人提供）：在出生后的早期大脑发育过程中，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)平衡的紊乱会引起异常活动，如癫痫发作和皮层发育异常。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，成人皮质神经元中E-I平衡的确切性质以及E-I平衡建立和维持的具体机制在很大程度上是未知的。记录功能性电路中E和I协调变化的全电路研究很少。我们的长期目标是利用啮齿动物的须-桶系统来了解桶皮层中发育中的抑制网络如何适应来自须的感觉输入，并维持它们与皮层兴奋网络的平衡。利用创新的小鼠遗传学和通道视紫红质辅助电路靶向，本研究将研究在出生后发育的敏感时期，兴奋性(E)和抑制性(I)突触之间的感觉活动是否参与调节E-I平衡。该建议的一个主要进展是提供了关于通路和输入特定的E/I平衡及其通过感官体验的差异调节的新信息。由于体内的网络加工是由特定输入驱动的，因此了解输入对E-I平衡及其成熟的特定调节具有重要意义。如果成功，这一提议将产生新的数据和假设

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.