International Research Fellowship Program: The Role of Gap-Junction Mediated Synchrony in Sensory Information Processing

[0804305]国际研究奖学金项目使美国科学家和工程师能够到国外进行9至24个月的研究。该计划的奖励为联合研究提供了机会，并利用独特或互补的设施、专业知识和国外的实验条件。该奖项将支持John Apergis-Schoute博士与Simon Schultz博士在英国伦敦帝国理工学院进行为期24个月的研究。理解大脑如何将物理世界转化为感知经验是现代神经科学的一个核心问题。通过对初级感觉皮质功能结构的分析，研究表明许多感觉编码的基本原理在不同的感觉模态中是保守的。例如，大多数感觉皮层的结构决定了有关感觉世界的信息分布在解剖学上不同的皮层位置。那么，大脑皮层是如何将这些支离破碎的感觉表征连接成一个统一的感知呢？一个重要的线索是，神经元对之间的同步是由刺激来调节的，刺激可以有效地驱动它们。这种同步性被认为是“粘合剂”。是通过支持低层次的连接感觉编码还是？颞绑定吗?。这两种模型背后的一种流行的机制理论认为，间隙连接耦合的中间神经元通过快速同步皮层域的节律性活动来支持感觉整合。然而，由于选择性记录已鉴定的中间神经元在体内的局限性，大多数关于间隙连接偶联中间神经元的结论？对网络功能的贡献来自于网络功能受损的研究。使用麻醉的转基因小鼠，其神经元表达间隙连接蛋白连接蛋白36 (Cx36)，在体内表达黄色荧光蛋白（YFP）， PI和宿主将监测Cx36-YFP神经元视觉驱动的细胞内和细胞旁信号。具体来说，他们将首先计划确定Cx36神经元在皮层网络中的身份和位置如何导致它们的感受野特性。这将通过比较Cx36神经元的化学成分和细胞形态及其视觉反应特性来实现。接下来，他们将评估间隙连接耦合的中间神经元与使用多电极阵列监测的V1网络活动之间的时间关系。信息论分析将使我们能够直接比较不同细胞类型对刺激结构整体相互信息的贡献。最后，他们的目标是通过向单个神经元注射电流来调节cx36偶联网络的兴奋性，从而改变皮层网络中视觉驱动的活动模式。这些实验将使他们能够统一大量的解剖学、生理学和理论工作，旨在理解刺激依赖同步的起源，并最终帮助他们理解这些过程如何促进感知的产生。

0804305Apergis-SchouteThe International Research Fellowship Program enables U.S. scientists and engineers to conduct nine to twenty-four months of research abroad. The program's awards provide opportunities for joint research, and the use of unique or complementary facilities, expertise and experimental conditions abroad.This award will support a twenty-four month research fellowship by Dr. John Apergis-Schoute to work with Dr. Simon Schultz at Imperial College in London, UK.Understanding how the brain transforms the physical world into perceptual experience is a central question in modern neuroscience. Through analysis of the functional architecture of primary sensory cortices, research has shown that many fundamental principles of sensory encoding are conserved across sensory modalities. For example, the architecture of most sensory cortices dictates that information regarding the sensory world is distributed across anatomically distinct cortical locations. But how then does the cortex link these fractured sensory representations into a unified percept? An important clue is that synchrony between neuronal pairs is modulated by stimuli which drive them both effectively. Such synchrony has been proposed to be the ?glue? of perceptual integration, either by supporting low-level conjunctive sensory coding or ?temporal binding?. A prevailing mechanistic theory behind both models states that gap junction-coupled interneurons support sensory integration by quickly synchronizing rhythmic activity across cortical domains. However, due to limitations in selectively recording from identified interneurons in vivo, most conclusions regarding gap junction-coupled interneurons? contributions to network function have come from studies where network function was compromised. Using anaesthetized transgenic mice whose neurons expressing the gap junction protein connexin-36 (Cx36) somatically express yellow-fluorescent protein (YFP) the PI and host will monitor visually-driven intra- and juxtacellular signals from Cx36-YFP neurons. Specifically, they will first plan on determining how the identity and position of Cx36 neurons within the cortical network results in their receptive field properties. This will be achieved by comparing the chemical composition and cellular morphology of Cx36 neurons with their visual response properties. Next, they will assess the temporal relation between gap junction-coupled interneurons and V1 network activity monitored using multi-electrode arrays. Information-theoretic analyses will allow us to directly compare the contributions made by different cell types to the overall mutual information regarding stimulus structure. Finally, they aim to modify visually-driven activity patterns in cortical networks by modulating the excitability of Cx36-coupled networks via current injections into individual neurons. These experiments will allow them to unify a large body of anatomical, physiological, and theoretical work aimed at understanding the origin of the stimulus-dependent synchrony, and ultimately, to help them understand how these processes contribute to the way perceptions arise.