Proteomics, Actin and Plasticity in Circadian Rhythms

大脑如何对经验进行编码，从而改变未来的行为？从学习到记忆修改，再到重置生物钟，这些大脑过程的特征都是神经功能的改变，生物钟在昼夜循环中形成行为变化的模式。潜在的机制尚不清楚。刺激诱导的以肌动蛋白为基础的细胞结构的重塑重新分配了结合在那里的关键信息蛋白，这一共识正在形成。哪些蛋白质介导了这种变化？研究人员将利用哺乳动物生物钟的力量，包括可塑性在内的机制在进化上是古老而保守的，日常行为的节律性稳态模式控制在一个大脑部位，即视交叉上核（SCN）。他们将采用跨学科的方法，结合新的分析化学，能够大规模分析和识别局部大脑区域的肌动蛋白结合蛋白与神经生理学和行为。研究人员将操纵SCN肌动蛋白状态，比较自然神经信号对肌动蛋白相关蛋白的影响与直接激活或抑制肌动蛋白重塑的试剂。这种广泛的方法将允许发现昼夜神经和行为可塑性所必需的蛋白质复杂性。结合蛋白质组学和功能分析将为如何将感官体验整合到跨越分子，细胞，大脑和行为水平的持久反应中提供新的见解。对这一进化上古老的大脑系统的研究将确定一组核心可塑性元素，这些元素可能对所有形式的大脑可塑性产生关键的涌现特性。因此，这些发现将影响对经验诱导的大脑适应的基本原理的理解。除了科学探究之外，这项研究将为实验室的学生提供分析化学和神经科学交叉的培训机会，并向本科生，特别是在科学领域代表性不足的少数民族提供培训机会。

How does the brain encode experience so that future behaviors are changed? Altered neural function that long outlasts experience characterizes brain processes from learning to memory modification to resetting the circadian clock, which patterns behavioral changes over the day-night cycle. Underlying mechanisms are not understood. Consensus is emerging that stimulus-induced remodeling of the actin-based cellular architecture redistributes key informational proteins bound there. Which proteins mediate this change? The researcher will use the power of the mammalian circadian clock, where mechanisms, including plasticity, are evolutionarily ancient and conserved, and control of the rhythmic homeostatic patterning of daily behaviors is localized within one brain site, the suprachiasmatic nucleus (SCN). They will employ a cross-disciplinary approach, combining novel analytical chemistry that enables large-scale analysis and identification of actin-binding proteins in local brain regions with neurophysiology and behavior. The researcher will manipulate SCN actin state, comparing effects of natural neural signals on actin-associated proteins with reagents that directly activate or inhibit actin remodeling. This broad approach will permit discovery of protein complexity necessary for circadian neural and behavioral plasticity. Coupled proteomic and functional analyses will provide new insights on how sensory experience is integrated into a long-lasting response spanning molecular, cellular, brain and behavioral levels. Research on this evolutionarily ancient brain system will identify a set of core plasticity elements that may contribute critical emergent properties to all forms of brain plasticity. Thus, findings will impact understanding of fundamental principles of experience-induced brain adaptation. Beyond scientific inquiry, this study will provide training opportunities at the intersection of analytical chemistry and neuroscience for students in the laboratory, as well as outreach to undergraduates, especially minorities under-represented in science.