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The effects of ethanol on short-term and long-term memory in Caenorhabditis elegans Butterfield, Michael

Abstract

In this thesis I have used the model organism Caenorhabditis elegans to investigate the effects of ethanol exposure on learning and memory. In the first part of this thesis I identified how ethanol affects the formation of long-term memory for habituation training. I administered ethanol during long-term memory training and found that high doses of ethanol significantly impair the formation of long-term memory. Next, I examined if ethanol was having an effect on the kinetics of short-term habituation and I found that ethanol exposure significantly altered the rate of habituation when stimuli were administered at longer interstimulus intervals (ISI) but was relatively unaffected at shorter ISIs. Interestingly, we found that the effect of ethanol on long-term memory formation was dissociable from the impairments on the rate of habituation and was not a state-dependent nor context-dependent deficit. Further, increased tolerance to ethanol did not rescue this deficit in memory formation and ethanol exposure did not disrupt previously formed memories. Since glutamatergic neurotransmission has been shown to be disrupted by ethanol exposure and the role of glr-1, a non-NMDA-type glutamate receptor subunit, in long-term memory for habituation has been extensively researched, I investigated whether the effects of ethanol on long-term memory formation involves gIr-1. Using a transgenic strain of worms that has GLR-1 tagged with a green fluorescent protein (GLR-1::GFP) I found that ethanol exposure results in an increase in the amount GLR-1: :GFP along the posterior ventral nerve cord. Further, 24 hrs following habituation training, trained unexposed worms show decreased levels of GLR-1::GFP while ethanol exposed trained worms are not significantly different from control groups. This result suggests that ethanol exposure not only causes increases in the level of GLR-1::GFP but also causes changes in glr-1 regulation that is normally associated with memory formation. In this thesis I have demonstrated that C. elegans is an ideal model system in which to study the effects of ethanol on learning and memory and have uncovered some important mechanisms mediating these effects.

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