Event Title

The Role of Ubiquitin-proteasome System in Regulation of Protein Synthesis and Memory Formation

Mentor 1

Dr. Fred Helmstetter

Location

Union Wisconsin Room

Start Date

24-4-2015 10:30 AM

End Date

24-4-2015 11:45 AM

Description

Previous work from our lab has shown that de novo protein synthesis as well as protein degradation mediated by the ubiquitin-proteasome system (UPS) are required for memory consolidation following several types of learning. Additional work from our lab suggests that UPS-mediated protein degradation may regulate mechanisms of protein synthesis during memory consolidation. Based on this information we attempted to identify specific molecules associated with de novo protein synthesis that may be regulated by proteasome activity during consolidation. Rats were trained with delay fear conditioning, consisting of 4 pairings of an auditory conditioned stimulus (CS) with a foot shock unconditioned stimulus(US). Following training, cannulated animals were given intra-amygdala injections of the proteasome inhibitor clasto-lactacystin-β-lactone (BLAC) or vehicle (2% DMSO in aCSF). Sixty minutes following injections the rats were euthanized and their brains were removed for tissue dissection. Amygdala tissue was isolated and analyzed using western blots. We specifically evaluated the phosphorylation status of substrates within the mammalian target of rapamycin (mTOR) and extra-cellular signal regulated kinase (ERK) pathways, given their involvement in protein synthesis initiation and memory consolidation. For this reason, we expect to find a decreased level of phosphorylation in the BLAC group compared to vehicle of effectors previously known to show increased levels of phosphorylation following training. Identifying specific effectors will give information on how protease activity is related to de novo protein synthesis and formation of memories.

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Apr 24th, 10:30 AM Apr 24th, 11:45 AM

The Role of Ubiquitin-proteasome System in Regulation of Protein Synthesis and Memory Formation

Union Wisconsin Room

Previous work from our lab has shown that de novo protein synthesis as well as protein degradation mediated by the ubiquitin-proteasome system (UPS) are required for memory consolidation following several types of learning. Additional work from our lab suggests that UPS-mediated protein degradation may regulate mechanisms of protein synthesis during memory consolidation. Based on this information we attempted to identify specific molecules associated with de novo protein synthesis that may be regulated by proteasome activity during consolidation. Rats were trained with delay fear conditioning, consisting of 4 pairings of an auditory conditioned stimulus (CS) with a foot shock unconditioned stimulus(US). Following training, cannulated animals were given intra-amygdala injections of the proteasome inhibitor clasto-lactacystin-β-lactone (BLAC) or vehicle (2% DMSO in aCSF). Sixty minutes following injections the rats were euthanized and their brains were removed for tissue dissection. Amygdala tissue was isolated and analyzed using western blots. We specifically evaluated the phosphorylation status of substrates within the mammalian target of rapamycin (mTOR) and extra-cellular signal regulated kinase (ERK) pathways, given their involvement in protein synthesis initiation and memory consolidation. For this reason, we expect to find a decreased level of phosphorylation in the BLAC group compared to vehicle of effectors previously known to show increased levels of phosphorylation following training. Identifying specific effectors will give information on how protease activity is related to de novo protein synthesis and formation of memories.