title: Distinct neurobehavioral dysfunction based on the timing of developmental binge-like alcohol exposure.
abstract: Gestational exposure to alcohol can result in long-lasting behavioral deficiencies generally described as fetal alcohol spectrum disorder (FASD). FASD-modeled rodent studies of acute ethanol exposure typically select one developmental window to simulate a specific context equivalent of human embryogenesis, and study consequences of ethanol exposure within that particular developmental epoch. Exposure timing is likely a large determinant in the neurobehavioral consequence of early ethanol exposure, as each brain region is variably susceptible to ethanol cytotoxicity and has unique sensitive periods in their development. We made a parallel comparison of the long-term effects of single-day binge ethanol at either embryonic day 8 (E8) or postnatal day 7 (P7) in male and female mice, and here demonstrate the differential long-term impacts on neuroanatomy, behavior and in vivo electrophysiology of two systems with very different developmental trajectories. The significant long-term differences in odor-evoked activity, local circuit inhibition, and spontaneous coherence between brain regions in the olfacto-hippocampal pathway that were found as a result of developmental ethanol exposure, varied based on insult timing. Long-term effects on cell proliferation and interneuron cell density were also found to vary by insult timing as well as by region. Finally, spatial memory performance and object exploration were affected in P7-exposed mice, but not E8-exposed mice. Our physiology and behavioral results are conceptually coherent with the neuroanatomical data attained from these same mice. Our results recognize both variable and shared effects of ethanol exposure timing on long-term circuit function and their supported behavior.
authors.affiliation: Department of Child and Adolescent Psychiatry, NYU School of Medicine, New York, NY, United States; Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, United States. Electronic address: Benjamin.Sadrian@nyumc.org.
authors.forename: B
authors.initials: B
authors.lastname: Sadrian
authors.affiliation: Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, United States.
authors.forename: M
authors.initials: M
authors.lastname: Lopez-Guzman
authors.affiliation: Department of Child and Adolescent Psychiatry, NYU School of Medicine, New York, NY, United States; Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, United States.
authors.forename: D A
authors.initials: DA
authors.lastname: Wilson
authors.affiliation: Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, United States; Department of Psychiatry, NYU School of Medicine, New York, NY, United States.
authors.forename: M
authors.initials: M
authors.lastname: Saito
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D063425:Binge Drinking / Q000473:pathology / Q000503:physiopathology*; D001921:Brain / Q000187:drug effects* / Q000254:growth & development* / Q000473:pathology / Q000503:physiopathology; D002492:Central Nervous System Depressants / Q000633:toxicity*; D004195:Disease Models, Animal; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D007395:Interneurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D008810:Mice, Inbred C57BL; D009434:Neural Pathways / Q000187:drug effects / Q000254:growth & development / Q000473:pathology / Q000503:physiopathology; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology; D055696:Olfactory Perception / Q000187:drug effects / Q000502:physiology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D065852:Spatial Memory / Q000187:drug effects / Q000502:physiology
chemical_list: D002492:Central Nervous System Depressants; D000431:Ethanol
keywords: FASD; hippocampus; neural circuit development; parvalbumin; piriform