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Teratogenic Effects of Ethanol on Layer VI Pyramidal Neurons in the Medial Prefrontal Cortex

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dc.contributor.advisor Bailey, Craig
dc.contributor.author Louth, Emma
dc.date.accessioned 2017-09-26T19:17:12Z
dc.date.available 2017-09-26T19:17:12Z
dc.date.copyright 2017-09
dc.date.created 2017-09-14
dc.date.issued 2017-09-26
dc.identifier.uri http://hdl.handle.net/10214/11617
dc.description.abstract Chronic exposure to ethanol during development can induce a wide variety of teratogenic effects. These effects may include craniofacial abnormalities, growth deficiencies and neurocognitive deficits, which in humans all fall under the umbrella term of Fetal Alcohol Spectrum Disorders (FASD). Neurocognitive deficits rank among the most common components of FASD and are particularly exemplified by the onset of attention deficits. However, the underlying neural mechanisms of these attention deficits in FASD are not known. Pyramidal neurons in layer VI of the medial prefrontal cortex (mPFC) play an important role in normal attention and effects of developmental ethanol exposure on this neuronal population have not been characterized. It was hypothesized that chronic developmental ethanol exposure impairs attention by persistently disrupting the development and mature function of layer VI pyramidal neurons in the mPFC. The mouse was used as the laboratory animal model for mammalian brain development in this thesis. First, long-term effects of developmental ethanol exposure were characterized in adult male mice, which included decreased performance on an attention task. This outcome was accompanied by alterations to the physiology and morphology of mPFC layer VI neurons, which exhibited decreased intrinsic excitability, increased responses to stimulation of nicotinic acetycholine (nACh) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and decreased dendrite tree size. To better-understand the timing and mechanisms by which this adult phenotype emerges, near-term effects of developmental ethanol exposure on layer VI neurons were characterized in young postnatal mice. Here, developmental ethanol exposure did not affect neuron physiology in male mice and increased nACh receptor function in female mice. Developmental ethanol exposure decreased dendrite tree size in male mice to a lesser extent than that observed in adult male mice, and increased dendrite tree size in female mice. The emergence of more severe teratogenic effects in adulthood compared with young postnatal life suggests that developmental ethanol exposure alters the developmental trajectory of mPFC layer VI pyramidal neurons to alter their physiology and morphology in adulthood. This research provides novel insight into potential neural mechanisms that underlie attention deficits associated with FASD and opens the door to future research to develop therapeutic/intervention strategies. en_US
dc.description.sponsorship The Banting Research Foundation, NSERC, CFI, Ontario Graduate Scholarship Program, Ontario Veterinary College en_US
dc.language.iso en en_US
dc.rights Attribution 2.5 Canada *
dc.rights.uri http://creativecommons.org/licenses/by/2.5/ca/ *
dc.subject developmental ethanol exposure en_US
dc.subject fetal alcohol spectrum disorder en_US
dc.subject medial prefrontal cortex en_US
dc.subject nicotinic acetylcholine receptor en_US
dc.subject AMPA receptor en_US
dc.title Teratogenic Effects of Ethanol on Layer VI Pyramidal Neurons in the Medial Prefrontal Cortex en_US
dc.type Thesis en_US
dc.degree.programme Biomedical Sciences en_US
dc.degree.name Doctor of Philosophy en_US
dc.degree.department Department of Biomedical Sciences en_US
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