Changes in the strength of connections between neurons underlie information storage in the mammalian brain. Long-term potentiation (LTP) is a long-lasting form of synaptic plasticity that has been described extensively in the hippocampus, a brain structure that plays a key role in memory formation. The molecular events that realise the persistence of LTP are not well understood, but it is known to require protein synthesis. The aim of this thesis was to investigate synaptic protein expression during the late-phase of hippocampal LTP in freely moving rats.
LTP was induced in the perforant path input to the dentate gyrus of Sprague-Dawley rats using high-frequency electrical stimulation paradigms known to produce LTP that persists for many days. To focus on late-occurring events, and complement existing data sets, rats were sacrificed 48 h after LTP induction. A broad survey of synaptic proteins was conducted by two-dimensional gel electrophoresis using postsynaptic density (PSD) fractions. Over 200 protein spots were resolved, from which 163 individual proteins were identified by mass spectrometry. These included cytoskeletal proteins, signalling molecules, molecular chaperones and mitochondrial components, but no transmembrane receptor proteins were detected.
Few of the identified proteins were found to undergo significant changes in expression, although proteomic comparison of PSDs prepared from LTP-stimulated and control dentate gyri showed reduced expression of the three component proteins of the mitochondrial voltage-dependent anion channel. While these data complement earlier studies suggesting that the late-phase of LTP is associated with mitochondrial restructuring, they cannot alone explain the persistence of LTP. To directly test whether LTP persistence is associated with increased expression of presynaptic marker proteins, suggesting increased neurotransmitter release; and/or increased postsynaptic receptor expression, implicating an increase in postsynaptic contact area, a targeted approach using Western Blot analysis of dentate gyrus subcellular fractions was undertaken.
| Identifer | oai:union.ndltd.org:ADTP/207880 |
| Date | January 2008 |
| Creators | Kennard, Jeremy Thomas Timothy, n/a |
| Publisher | University of Otago. Department of Anatomy & Structural Biology |
| Source Sets | Australiasian Digital Theses Program |
| Language | English |
| Detected Language | English |
| Rights | http://policy01.otago.ac.nz/policies/FMPro?-db=policies.fm&-format=viewpolicy.html&-lay=viewpolicy&-sortfield=Title&Type=Academic&-recid=33025&-find), Copyright Jeremy Thomas Timothy Kennard |
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