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The effects of ethanol on the physical development, nervous system development and behaviour of Caenorhabditis elegans Davis, Justin Robert

Abstract

In this thesis I have used the nematode worm Caenorhabditis elegans to study the effects of ethanol exposure on basic physical development and on specific aspects of nervous system development and behaviour. In the first part of this thesis I investigated how chronic exposure to ethanol affects the physical development and life history of worms. I found that chronic exposure to ethanol negatively impacts C. elegans size, rate of development, reproductive fecundity and life expectancy. I further investigated how exposure to ethanol during embryonic development affects this system by exposing eggs to ethanol for 1 hour a different time points during embryogenesis. I found that embryos exposed acutely to ethanol early in their development have a lower probability of hatching into larval worms, and those worms that do hatch display distinct dysmorphologies. In the second part of the thesis I examined how chronic exposure to ethanol affects the C. elegans nervous system and behaviour. In this set of experiments I found the total amount of GFP expression of two different pan-neuronal genes was decreased relative to the size of worms as a result of chronic exposure to ethanol. To determine whether this decrease in apparent size of the nervous system due to ethanol exposure affected the behavior of adult worms I examined two simple, well-studied behaviours: tap withdrawal which is mediated in part by glutamatergic neurotransmission, and the basal slowing response which is mediated by dopaminergic neurotransmission. I found that chronic ethanol exposure attenuated the tap withdrawal response, but did not affect the basal slowing response. To investigate the effects of ethanol on the tap withdrawal circuit I examined the expression patterns of two genes that are expressed in the mechanosensory circuit. I found that the expression of GLR-1::GFP, a non-NMDA type glutamate receptor sub-unit expressed on the interneurons of the tapwithdrawal circuit, is increased as a result of chronic exposure to ethanol. I also found that the timing of the development of the post-embryonic mechanosensory cells is affected by chronic exposure to ethanol. Together these alterations in the tap circuit could have produced the behavioural changes observed. In this thesis I have characterized the effects of ethanol on the basic biology, nervous system and behaviour of C. elegans with the specific aim of generating data to support further investigations of the effects of ethanol on nervous system development and behaviour in this system.

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