title: Prenatal domoic acid exposure disrupts mouse pro-social behavior and functional connectivity MRI.
abstract: Domoic acid (DA) is a toxin produced by marine algae and known primarily for its role in isolated outbreaks of Amnestic Shellfish Poisoning and for the damage it inflicts on marine mammals, particularly California sea lions. Lethal effects of DA are often preceded by seizures and coma. Exposure to DA during development can result in subtle and highly persistent effects on brain development and include behavioral changes that resemble diagnostic features of schizophrenia and anomalies in social behavior we believe are relevant to autism spectrum disorder (ASD). To more fully examine this hypothesis, we chose to examine adolescent mice exposed in utero to DA for endpoints relevant to ASD, specifically changes in social behavior and network structure, the latter measured by resting state functional connectivity (rs-fcMRI). We found that male offspring exposed in utero to DA expressed reproducible declines in social interaction and atypical patterns of functional connectivity in the anterior cingulate, a region of the default mode network that is critical for social functioning. We also found disruptions in global topology in regions involved in the processing of reward, social, and sensory experiences. Finally, we found that DA exposed males expressed a pattern of local over-connectivity. These anomalies in brain connectivity bear resemblance to connectivity patterns in ASD and help validate DA-exposed mice as a model of this mental disability.
authors.affiliation: Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR 97239, United States.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Mills
authors.affiliation: Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR 97239, United States.
authors.forename: Hadley L
authors.initials: HL
authors.lastname: Pearce
authors.affiliation: Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR 97239, United States.
authors.forename: Omar
authors.initials: O
authors.lastname: Khan
authors.affiliation: Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR 97239, United States.
authors.forename: Ben R
authors.initials: BR
authors.lastname: Jarrett
authors.affiliation: Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR 97239, United States; Department of Psychiatry, Oregon Health & Science University, Portland, OR 97239, United States; Advanced Imaging Research Center, Oregon Health & Science University, Portland, OR 97239, United States.
authors.forename: Damien A
authors.initials: DA
authors.lastname: Fair
authors.affiliation: Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR 97239, United States. Electronic address: lahvisg@ohsu.edu.
authors.forename: Garet P
authors.initials: GP
authors.lastname: Lahvis
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001931:Brain Mapping; D005260:Female; D007091:Image Processing, Computer-Assisted; D007608:Kainic Acid / Q000031:analogs & derivatives* / Q000633:toxicity; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008959:Models, Neurological; D009434:Neural Pathways / Q000000981:diagnostic imaging*; D009498:Neurotoxins / Q000633:toxicity*; D010100:Oxygen / Q000097:blood; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000503:physiopathology; D012146:Rest; D012201:Reward; D012919:Social Behavior; D012920:Social Behavior Disorders / Q000139:chemically induced* / Q000000981:diagnostic imaging; D014828:Vocalization, Animal / Q000187:drug effects
chemical_list: D009498:Neurotoxins; C012301:domoic acid; D010100:Oxygen; D007608:Kainic Acid
keywords: Autism; Brain imaging; Mouse; Resting state functional connectivity; Social behavior