Medium Spiny Neurons (MSNs) are the primary cell type of the striatum, a
structure critically involved in motivation, memory, and movement. MSN structure and
function are altered in Parkinson’s and Huntington’s disease as well as following
repeated exposure to drugs of abuse. One site on the MSN that changes in all of these
diseases is the dendritic spine, a sub-micron protrusion responsible for receiving
excitatory (glutamatergic) signals. Dendritic spines undergo structural and functional
changes during development, normal aging, and disease. To date, no studies have
specifically characterized the developmental changes undergone by MSN dendritic spines
and investigation into the molecules that regulate MSN dendritic spines has been limited
to in vivo manipulations in adults or characterization of global knockout of specific
molecules. Research into MSN dendritic spine development and plasticity mechanisms
were likely limited by the absence of an in vitro primary neuronal culture system that produced MSNs with mature in vivo-like characteristics. The experiments detailed in this
thesis describe the development and characterization of such a system as well as a
morphological analysis of MSN development in culture. MSNs cultured using this
technique develop gross morphological characteristics similar to in vivo cells. They also
develop high densities of dendritic spines with a high variety of mature morphologies and
have synaptic and intrinsic physiological characteristics like MSNs in vivo. This work
represents a significant contribution to the field, supporting future research into the
molecules that regulate MSN development and plasticity in both normal and disease
University of Minnesota Ph.D. dissertation. May 2012. Major: Neuroscience. Advisors:Dr. Lorene Lanier, Dr. Mark Thomas. 1 computer file (PDF); viii, 115 pages.
Penrod-Martin, Rachel Dobrof.
Morphological characterization of medium spiny neuron development in vitro.
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