Mechanisms of Dendritic Spine Stability

描述(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的信号处理中发挥关键作用的小突触后结构。脊椎数量和形状的破坏在许多神经和神经精神疾病中都会发生，包括情绪障碍、自闭症和神经退行性疾病。脊柱的大小和形状与突触的生理强度相关，因此了解调节脊柱形状和稳定性的关键分子通路对于设计对抗此类认知疾病的疗法至关重要。这个项目将集中在控制脊柱形状和稳定性的中央分子途径，涉及到蛋白质Marcks。在分离的啮齿动物神经元培养中使用定量荧光成像，该项目将使用细胞和分子方法表征树突棘中Marcks的功能。项目目标是确定Marcks与下游效应器的相互作用及其对肌动蛋白细丝和突触蛋白组装的影响。与公共健康相关：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的信号处理中发挥关键作用的小突触后结构。脊椎数量和形状的破坏在许多神经和神经精神疾病中都会发生，包括情绪障碍、自闭症、中风和神经退行性疾病。脊柱的大小和形状与突触的生理强度相关，因此了解调节脊柱形状和稳定性的关键分子通路对于设计对抗此类认知疾病的疗法至关重要。这个项目将集中在控制脊柱形状和稳定性的中央分子途径，涉及蛋白质Marcks和信号磷脂PIP2。在分离的啮齿动物神经元培养中使用定量荧光成像，该项目将使用细胞和分子方法表征树突棘中Marcks的功能。项目目标是确定Marcks与下游效应器的相互作用及其对肌动蛋白细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.