title: Developmental Ethanol Exposure Leads to Long-Term Deficits in Attention and Its Underlying Prefrontal Circuitry.
abstract: Chronic prenatal exposure to ethanol can lead to a spectrum of teratogenic outcomes that are classified in humans as fetal alcohol spectrum disorders (FASD). One of the most prevalent and persistent neurocognitive components of FASD is attention deficits, and it is now thought that these attention deficits differ from traditional attention deficit hyperactivity disorder (ADHD) in their quality and response to medication. However, the neuronal mechanisms underlying attention deficits in FASD are not well understood. We show here that after developmental binge-pattern ethanol exposure, adult mice exhibit impaired performance on the five-choice serial reaction time test for visual attention, with lower accuracy during initial training and a higher rate of omissions under challenging conditions of high attention demand. Whole-cell electrophysiology experiments in these same mice find dysregulated pyramidal neurons in layer VI of the medial prefrontal cortex, which are critical for normal attention performance. Layer VI neurons show decreased intrinsic excitability and increased responses to stimulation of both nicotinic acetylcholine receptors and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptors. Moreover, although nicotinic acetylcholine responses correlate with performance on the five-choice task in control mice, these relationships are completely disrupted in mice exposed to ethanol during development. These findings demonstrate a novel outcome of developmental binge-pattern ethanol exposure and suggest that persistent alterations to the function of prefrontal layer VI neurons play an important mechanistic role in attention deficits associated with FASD.
authors.affiliation: Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph , Guelph, Ontario N1G 2W1, Canada.
authors.forename: Emma L
authors.identifier: 0000-0001-5357-1315
authors.initials: EL
authors.lastname: Louth
authors.affiliation: Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph , Guelph, Ontario N1G 2W1, Canada.
authors.forename: Warren
authors.initials: W
authors.lastname: Bignell
authors.affiliation: Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph , Guelph, Ontario N1G 2W1, Canada.
authors.forename: Christine L
authors.identifier: 0000-0002-4398-7429
authors.initials: CL
authors.lastname: Taylor
authors.affiliation: Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph , Guelph, Ontario N1G 2W1, Canada.
authors.forename: Craig D C
authors.identifier: 0000-0002-4320-6872
authors.initials: CD
authors.lastname: Bailey
mesh_terms: D000818:Animals; D001288:Attention / Q000502:physiology*; D063425:Binge Drinking; D002492:Central Nervous System Depressants / Q000633:toxicity; D004195:Disease Models, Animal; D000431:Ethanol / Q000633:toxicity; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000503:physiopathology* / Q000523:psychology*; D008297:Male; D008810:Mice, Inbred C57BL; D009434:Neural Pathways / Q000187:drug effects / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000254:growth & development / Q000503:physiopathology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011897:Random Allocation; D018091:Receptors, AMPA / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000378:metabolism; D046509:Tissue Culture Techniques
chemical_list: D002492:Central Nervous System Depressants; D018091:Receptors, AMPA; D011978:Receptors, Nicotinic; D000431:Ethanol
keywords: attention; developmental ethanol exposure; electrophysiology; fetal alcohol spectrum disorders; nicotinic receptors; prefrontal cortex