Prenatal domoic acid exposure disrupts mouse pro-social behavior and functional connectivity MRI

Brian D. Mills, Hadley L. Pearce, Omar Khan, Ben R. Jarrett, Damien Fair, Garet Lahvis

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)14-23
Number of pages10
JournalBehavioural Brain Research
Volume308
DOIs
StatePublished - Jul 15 2016

Fingerprint

Social Behavior
Magnetic Resonance Imaging
Gyrus Cinguli
Marine Toxins
Sea Lions
Shellfish Poisoning
Brain
Interpersonal Relations
Coma
domoic acid
Reward
Social Support
Disease Outbreaks
Mammals
Schizophrenia
Seizures
Autism Spectrum Disorder

Keywords

  • Autism
  • Brain imaging
  • Mouse
  • Resting state functional connectivity
  • Social behavior

ASJC Scopus subject areas

  • Behavioral Neuroscience

Cite this

Prenatal domoic acid exposure disrupts mouse pro-social behavior and functional connectivity MRI. / Mills, Brian D.; Pearce, Hadley L.; Khan, Omar; Jarrett, Ben R.; Fair, Damien; Lahvis, Garet.

In: Behavioural Brain Research, Vol. 308, 15.07.2016, p. 14-23.

Research output: Contribution to journalArticle

Mills, Brian D. ; Pearce, Hadley L. ; Khan, Omar ; Jarrett, Ben R. ; Fair, Damien ; Lahvis, Garet. / Prenatal domoic acid exposure disrupts mouse pro-social behavior and functional connectivity MRI. In: Behavioural Brain Research. 2016 ; Vol. 308. pp. 14-23.
@article{f5b0aa8e84f644a1a50162f462db00b0,
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.",
keywords = "Autism, Brain imaging, Mouse, Resting state functional connectivity, Social behavior",
author = "Mills, {Brian D.} and Pearce, {Hadley L.} and Omar Khan and Jarrett, {Ben R.} and Damien Fair and Garet Lahvis",
year = "2016",
month = "7",
day = "15",
doi = "10.1016/j.bbr.2016.03.039",
language = "English (US)",
volume = "308",
pages = "14--23",
journal = "Behavioural Brain Research",
issn = "0166-4328",
publisher = "Elsevier",

}

TY - JOUR

T1 - Prenatal domoic acid exposure disrupts mouse pro-social behavior and functional connectivity MRI

AU - Mills, Brian D.

AU - Pearce, Hadley L.

AU - Khan, Omar

AU - Jarrett, Ben R.

AU - Fair, Damien

AU - Lahvis, Garet

PY - 2016/7/15

Y1 - 2016/7/15

N2 - 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.

AB - 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.

KW - Autism

KW - Brain imaging

KW - Mouse

KW - Resting state functional connectivity

KW - Social behavior

UR - http://www.scopus.com/inward/record.url?scp=84963537493&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84963537493&partnerID=8YFLogxK

U2 - 10.1016/j.bbr.2016.03.039

DO - 10.1016/j.bbr.2016.03.039

M3 - Article

C2 - 27050322

AN - SCOPUS:84963537493

VL - 308

SP - 14

EP - 23

JO - Behavioural Brain Research

JF - Behavioural Brain Research

SN - 0166-4328

ER -