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Plasticity of behaviours modulated by alcohol Lin, Conny Hsin-Cheng

Abstract

In this dissertation, I investigated the ways that alcohol modulates plasticity of behaviours through studying effects of alcohol on body posture, locomotion, and a simple form of behavioral plasticity, habituation, in the genetic model organism Caenorhabditis elegans. I found that the effects of alcohol on body posture and locomotion are temporally dynamic especially for the first 30 min. Some earlier studies found alcohol facilitated habituation but others found alcohol inhibited habitation. I found that alcohol can both facilitate or inhibit habituation of the reversal response to repeated stimuli (taps) depending on the component of the reversal response assessed. Furthermore, I discovered that alcohol altered the predominant response to tap from a backward reversal to a forward acceleration. With this understanding, I examined the role of 27 genes on the alcohol induced behavioural changes characterized in Chapter 2. I found different alcohol modulated behaviors involved different sets of genes. For example, I observed that 2 genes modulated only body posture, 3 genes modulated only reversals, 1 gene modulated posture and acceleration but not reversal. I also discovered a gene not previously implicated in alcohol’s effect on behaviour: tomosyn, a negative regulator of SNARE complex. In the final study I investigated another alcohol modulated behavioural plasticity: tolerance. In C. elegans acute tolerance has been studied, however, chronic tolerance has not. I developed a chronic alcohol exposure paradigm and tested several candidate genes to determine whether they play a role in chronic tolerance to alcohol. I found that worms with a mutation in the Neuropeptide Y receptor, a gene that is involved in acute tolerance, had better chronic tolerance than wild-type worms. I then showed that mutations in genes that encode histone methyltransferases impaired chronic tolerance, which provided the first evidence relating histone methyltransferases with functional outcomes of alcohol exposure in adult animals. Together, the results from my dissertation contribute to our understanding of how alcohol alters behaviour.

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