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.

Public Health Relevance

The goal of this project is to understand the mechanisms by which the developing cortical inhibitory networks are able to adapt to sensory input from the whiskers, and to maintain their balance with cortical excitatory networks.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Academic Research Enhancement Awards (AREA) (R15)
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Special Emphasis Panel (ZRG1-MDCN-A (96))
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Gnadt, James W
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University of Wyoming
Schools of Arts and Sciences
United States
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Sun, Qian-Quan; Wang, Xinjun; Yang, Weiguo (2014) Laserspritzer: a simple method for optogenetic investigation with subcellular resolutions. PLoS One 9:e101600
Wang, Xinjun; Hooks, Bryan M; Sun, Qian-Quan (2014) Thorough GABAergic innervation of the entire axon initial segment revealed by an optogenetic 'laserspritzer'. J Physiol 592:4257-76