Local Control of Synaptic Strength: Neurotrophic and Dopaminergic Modulation of Dendritic Protein Synthesis

Citation

Smith, W. Bryan (2004) Local Control of Synaptic Strength: Neurotrophic and Dopaminergic Modulation of Dendritic Protein Synthesis. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/15vm-zk49. https://resolver.caltech.edu/CaltechETD:etd-05262004-125208

Abstract

Understanding the cell biological mechanisms responsible for the plasticity of central neurons is key to our understanding of brain function. In an effort to better characterize the cell and molecular biology of individual neurons, we have studied the role of local, dendritic protein synthesis in hippocampal synaptic plasticity. Such a localized control of protein synthesis provides a means of achieving input-specificity, the observation that synapses on a given neuron are able to independently scale the strength of their connections. This property of synaptic enhancement is correlated with the encoding capacity of an individual cell: the greater the input specificity, the more information a cell can encode.

Here we show two pathways for inducing local protein synthesis, one mediated by the brain-derived neurotrophic factor, and another by the D1/D5 dopaminergic signaling system. Local protein synthesis stimulated by the dopaminergic pathway leads directly to an increase in synaptic strength by increasing production and synaptic localization of AMPA receptors, the glutamate-gated ion channels that mediate fast synaptic transmission at central synapses. We also present a set of software tools for quantitative analysis of 3-D colocalization and 2-D spatial correlation in immunofluorescence microscopy. These tools will greatly assist in exploratory data analysis of the dynamics of protein distributions in neurons and other cells.

Thesis Files