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Identification of genes associated with late-phase long-term potentiation in the hippocampal Schaffer-CA1 pathway

Posted on:2004-10-15Degree:Ph.DType:Dissertation
University:The University of Texas at San AntonioCandidate:Peng, HaixiangFull Text:PDF
GTID:1464390011969099Subject:Biology
Abstract/Summary:
The long-term potentiation (LTP), an activity-dependent long-lasting form of synaptic plasticity, is considered the best model for understanding mechanisms underlying learning and memory. The maintenance of LTP depends on alteration of gene transcription. By screening a subtracted cDNA library that is enriched in up-regulated transcripts in rat hippocampus 3 hours following Schaffer-CA1 LTP induction in vivo, 39 genes were identified, including SCG10, a neural growth-associated protein. The differential expression of SCG10 mRNA was quantified by relative RT-PCR and Northern blot analysis. In situ hybridization with a probe targeting a 2kb SCG10 mRNA demonstrated an increase of SCG10 expression in the ipsilateral CA3 and CA1 areas, but not their contralateral counterparts or either side of dentate gyrus. The time-course study using semi-quantitative real-time RT-PCR showed that SCG10 1 and 2kb transcripts increased only at 3 hours, but not at 1 or 24 hours. These results suggest that SCG10 may play a role in maintenance of synaptic plasticity through a transient regulation of microtubule dynamics, which facilitate the structural remodeling of presynaptic element.; In the next approach, Affymetrix high-density oligonucleotide arrays were used to profile genes associated with Schaffer-CA1 LTP induced in vivo. Using rat neurobiology RNU34 arrays, both up- and down-regulated genes were identified, including some that encode proteins involved in synaptic plasticity, vesicular trafficking and recycling, transcription regulation, and cell-cell communication. In the following time-course study, the temporal gene expression patterns were profiled by using a rat Genome RGU34A arrays containing 8,799 genes/ESTs. The genes whose expression levels significantly changed at different time-points, i.e., 1, 3 or 24 hours after LTP induction, were identified by the one-way ANOVA (p < 0.05). These genes (1,583) were then grouped together based on the similarities of their expression patterns using cluster analysis. While the majority of genes (903) were up-regulated at 24 hours, only 94 genes showed higher expression at 1 hour. At 3 hours, expression levels of 257 genes were increased and 329 were decreased. These results have the potential to reveal functional relationships among genes with similar temporal expression patterns and may describe the cascade of cellular events underlying LTP.
Keywords/Search Tags:Genes, LTP, Expression, Synaptic plasticity, SCG10, Schaffer-ca1
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