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.
Bibliographical noteFunding Information:
This report was supported by the the following NIH grants: R01 DA02254 (Lahvis), R01 MH096773 (Fair), UL1TR000128 (Fair), and T32DA007262 (stipend support for BDM). This work was inspired by concurrent studies of California sea lions at The Marine Mammal Center (TMMC) that were supported by Oregon Sea Grant, NA06OAR4170059, project number R/BT-50-PD from the National Oceanic and Atmospheric Administration’s National Sea Grant College Program, U.S. Department of Commerce, and by appropriations made by the Oregon State Legislature (Lahvis).
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- Brain imaging
- Resting state functional connectivity
- Social behavior