Impaired and enhanced spatial representation of the PSD-95 knockout mouse
Name
56795379-MIT.pdf
Description
Full printable version
Size
14.94 MB
Format
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Checksum (MD5)
76eb00931888e08cdb0cd11dff259a1d
Author(s)
Sun, Linus Da-Shih, 1972-
Advisor(s)
Matthew A. Wilson.
Date Issued
2004
Publisher
Massachusetts Institute of Technology
Abstract
Postsynaptic density protein-95 (PSD-95) is the second most abundantly expressed synaptic protein in the postnatal forebrain. It is an integral part of the postsynaptic scaffolding complex and helps recruit receptors, channels and associated factors involved with synaptic transmission. A mouse whose wildtype gene was replaced with truncation mutant of PSD-95 preserving two PDZ binding domains causes a spatial learning and memory deficit and a dramatic enhancement of synaptic strengthening. Long Term Potentiation is enhanced at all frequencies of stimulation (1-100Hz), while Long Term Depression is absent in the mutants. This study explores CA1 pyramidal cell spatial representations in the PSD-95 mutant mice. Mutants are not significantly different than controls in running velocity. Nor are its pyramidal cells or interneurons different than controls in: place cell firing rates, sparsity of run active cells, bursting behavior, or theta modulated activity. However, mutants do exhibit significantly larger place fields and wider spike waveforms. Mutants also expressed enhanced directionality of place fields and increased post-run sleep correlation of firing for overlapping place fields. Mutants also exhibited disruption of asymmetrical place fields and phase precession, the first such observation reported in mice. In conclusion, LTP alone is not enough for the active process of encoding experience. Instead, bi-directional synaptic plasticity is necessary for proper place field formation, correlation, directionality, asymmetry, phase precession, and the formation of spatial memories.
Description
Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, June 2004.
Includes bibliographical references (p. 175-185).
Subjects
Biology.
MIT Department
Massachusetts Institute of Technology. Department of Biology
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