effect of Ras/MAPK signaling in the mouse hippocampus
Subtitle: a morphological examination of synaptic and dendritic alterations in CA1 (California).
Published: 2004
Language: eng
Number of pages: 162
Description: Considerable evidence has accumulated demonstrating that dendritic processes involved in synaptic plasticity are critical for learning and memory. However, little research has focused on presynaptic mechanisms underling learning and memory in mammals. The laboratory of Dr. Alcino Silva at the University of California at Los Angeles developed a RasG12V mouse model, and conducted experiments which exposed novel aspects of Ras function in post-mitotic neurons, by taking advantage of this mutation to increase signaling through the mitogen-activated protein kinase (MAPK) pathway. This mutant demonstrated enhanced long-term potentiation (LTP), enhanced behavioral learning, and a primarily presynaptic localization of this Ras isomer. The current research examined changes in spine and synaptic morphology that may underlie the types of neural plasticity observed in this mutant. No changes in synapse per neuron densities for total synapses, total macular synapses or total perforated synapses were observed in RasG12V as compared to wild-type (WT) mice. Electron and light microscopy analysis of hippocampal CA1 excitatory terminals revealed that the general appearance of presynaptic terminals, spines, and postsynaptic densities was similar in WT and RasG12V mice. There was however, in the RasG12V mutant, a significant increase in the density of docked vesicles, an increased proportion of concave perforated synapses, and an increased number of mushroom shaped spines. The current research suggests that the presynaptic signaling mechanisms associated with this mutant may modulate neural plasticity by increasing the size of the readily-releasable vesicular pool. However, while alterations in presynaptic vesicular docking may be the initial and primary mechanism underlying the electrophysiological and behavioral alterations in these animals, this change apparently has downstream effects, with an associated increase in the proportion of concave perforated synapses and mushroom spines. Taken together, these alterations in the mutant may account for the enhancements in LTP and learning previously observed, and suggest that alterations in these synaptic and dendritic morphological characteristics may play a critical role in LTP, and, learning and memory processes in general.
Notes: Adviser: Ted L. Petit.

Thesis (Ph.D.)--University of Toronto, 2004.

Electronic version licensed for access by U. of T. users.

Source: Dissertation Abstracts International, Volume: 65-05, Section: B, page: 2686.