A dendritic spine is a small membranous protrusion that extends from a dendrite and forms the postsynaptic half of an asymmetric synapse in the CNS. Most asymmetric synapses convey the excitatory information between neurons, and the function and structure of excitatory synapses are highly plastic under the influence of their activities. Virtually all excitatory synapses have a specialized postsynaptic electron-dense structure, called postsynaptic density (PSD), underneath the postsynaptic membrane, and the PSD contains receptors, signal transducing proteins, scaffold proteins and cytoskeletal proteins. This thesis consists of three parts. In the first part, I report a study of the mechanism regulating the localization of various cytoplasmic proteins in dendritic spines. This mechanism is dependent upon a dynamic microfilament cytoskeleton and sensitive to the mobilization of internal calcium stores and cold. The second part of this thesis describes the identification of the heavy chain of cytoplasmic dynein (cDHC) as a major component of the PSD fraction. The finding that both dynein heavy and intermediate chains are enriched in the PSD fraction and cDHC in dendritic spines raise the possibilities that cytoplasmic dynein may play structural and functional roles in the postsynaptic terminal. In the third part, I report the design and implementation of a temperature-controlling system for the use of observing live cells maintained on glass coverslip with an up-right confocal or epi-fluorescence microscope. Together, those findings and technological innovations will help to reveal the molecular mechanisms underlying the structure/function relationships of excitatory synapses and the morphological plasticity of dendritic spines.

A dendritic spine is a small membranous protrusion that extends from a dendrite and forms the postsynaptic half of an asymmetric synapse in the CNS. Most asymmetric synapses convey the excitatory information between neurons, and the function and structure of excitatory synapses are highly plastic under the influence of their activities. Virtually all excitatory synapses have a specialized postsynaptic electron-dense structure, called postsynaptic density (PSD), underneath the postsynaptic membrane, and the PSD contains receptors, signal transducing proteins, scaffold proteins and cytoskeletal proteins. This thesis consists of three parts. In the first part, I report a study of the mechanism regulating the localization of various cytoplasmic proteins in dendritic spines. This mechanism is dependent upon a dynamic microfilament cytoskeleton and sensitive to the mobilization of internal calcium stores and cold. The second part of this thesis describes the identification of the heavy chain of cytoplasmic dynein (cDHC) as a major component of the PSD fraction. The finding that both dynein heavy and intermediate chains are enriched in the PSD fraction and cDHC in dendritic spines raise the possibilities that cytoplasmic dynein may play structural and functional roles in the postsynaptic terminal. In the third part, I report the design and implementation of a temperature-controlling system for the use of observing live cells maintained on glass coverslip with an up-right confocal or epi-fluorescence microscope. Together, those findings and technological innovations will help to reveal the molecular mechanisms underlying the structure/function relationships of excitatory synapses and the morphological plasticity of dendritic spines.

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