Mechanisms of Dendritic Spine Stability

描述（由申请人提供）：该项目的长期目标是确定调节树突棘稳定性和可塑性的分子机制，树突棘是在神经元回路中信号处理中起关键作用的小突触后结构。脊柱数量和形状的破坏发生在许多神经和神经精神疾病中，包括情绪障碍、自闭症和神经退行性疾病。棘突的大小和形状与突触的生理强度相关，因此了解调节棘突形状和稳定性的关键分子通路对于设计治疗方法以对抗此类认知疾病至关重要。该项目将集中在一个中央分子通路控制脊柱的形状和稳定性，涉及蛋白质MARCKS。利用定量荧光成像在啮齿动物神经元的解离培养，该项目将表征MARCKS的功能，在树突棘使用细胞和分子的方法。项目目标是确定MARCKS与下游效应物的相互作用及其对肌动蛋白丝和突触蛋白组装的影响。公共卫生相关性：该项目的长期目标是确定调节树突棘的稳定性和可塑性的分子机制，树突棘是在神经元回路的信号处理中起关键作用的小突触后结构。脊柱数量和形状的破坏发生在许多神经和神经精神疾病中，包括情绪障碍、自闭症、中风和神经退行性疾病。棘突的大小和形状与突触的生理强度相关，因此了解调节棘突形状和稳定性的关键分子通路对于设计治疗方法以对抗此类认知疾病至关重要。该项目将重点关注控制脊柱形状和稳定性的中心分子途径，涉及蛋白质MARCKS和信号磷脂PIP2。利用定量荧光成像在啮齿动物神经元的解离培养，该项目将表征MARCKS的功能，在树突棘使用细胞和分子的方法。项目目标是确定MARCKS与下游效应物的相互作用及其对肌动蛋白丝和突触蛋白组装的影响。

DESCRIPTION (provided by applicant): The long-term goal of this project is to identify molecular mechanisms that regulate the stability and plasticity of dendritic spines, small postsynaptic structures that play key roles in signal processing in neuronal circuits. Disruptions of spine numbers and shape occur in many neurological and neuropsychiatric diseases, including mood disorders, autism, and neurodegenerative disease. The size and shape of spines correlates with the physiological strength of the synapse, thus understanding the key molecular pathways that regulate spine shape and stability are crucial for designing therapies to combat such cognitive diseases. This project will focus on a central molecular pathway controlling spine shape and stability that involves the protein MARCKS. Using quantitative fluorescence imaging in dissociated cultures of rodent neurons, the project will characterize the function of MARCKS in dendritic spines using cellular and molecular approaches. Project objectives are to identify the interaction of MARCKS with downstream effectors and their influence on actin filaments and synaptic protein assemblies. PUBLIC HEALTH RELEVANCE: The long-term goal of this project is to identify molecular mechanisms that regulate the stability and plasticity of dendritic spines, small postsynaptic structures that play key roles in signal processing in neuronal circuits. Disruptions of spine numbers and shape occur in many neurological and neuropsychiatric diseases, including mood disorders, autism, stroke, and neurodegenerative disease. The size and shape of spines correlates with the physiological strength of the synapse, thus understanding the key molecular pathways that regulate spine shape and stability are crucial for designing therapies to combat such cognitive diseases. This project will focus on a central molecular pathway controlling spine shape and stability that involves the protein MARCKS and the signaling phospholipid PIP2. Using quantitative fluorescence imaging in dissociated cultures of rodent neurons, the project will characterize the function of MARCKS in dendritic spines using cellular and molecular approaches. Project objectives are to identify the interaction of MARCKS with downstream effectors and their influence on actin filaments and synaptic protein assemblies.