Dissertation
Effects of prenatal disruptions on dorsal striatal development and relevant behavior in mice
University of Iowa
Doctor of Philosophy (PhD), University of Iowa
Spring 2025
DOI: 10.25820/etd.007842
Abstract
The dorsal striatum is implicated in multiple neurodevelopmental disorders, including autism spectrum disorder (ASD). Clinical studies of patients with ASD show striatal enlargement and changes in functional connectivity that display altered trajectories over time and correlate with symptoms, which we have described in a literature review. This evidence suggests that early developmental changes in the dorsal striatum may contribute to neurodevelopmental disorder symptomatology, making it a critical topic for research.
Using a prenatal stress mouse model of neurodevelopmental risk, we analyzed dorsal striatal outcomes in offspring on cellular, molecular, behavioral, and physiological levels. We did not observe changes in striatal volume or cellular composition, but we found significant ASD-relevant transcriptional changes in multiple striatal cell types through single-cell RNA sequencing. We also observed enhanced motor learning on rotarod and earlier switch times in an interval timing task, with the latter accompanied by altered time-related activity in medium spiny neurons. To investigate the observation of striatal enlargement in patients with ASD, we developed a mouse model of striatal overgrowth using prenatal administration of an mGluR5 agonist. Results indicated increased striatal cell density in the embryonic brain, and we reported abnormalities in postnatal development as well as adult striatal-dependent behaviors.
Together, these findings advance our understanding of the role of dorsal striatal development in ASD-relevant phenotypes. Results from the single-cell RNA sequencing experiment in particular may provide new mechanistic targets for future treatments for individuals with ASD and other neurodevelopmental disorders.
Details
- Title: Subtitle
- Effects of prenatal disruptions on dorsal striatal development and relevant behavior in mice
- Creators
- Maya M. Evans
- Contributors
- Hanna Stevens (Advisor)Sheila Baker (Committee Member)Marco Hefti (Committee Member)Nandakumar Narayanan (Committee Member)Aislinn Williams (Committee Member)
- Resource Type
- Dissertation
- Degree Awarded
- Doctor of Philosophy (PhD), University of Iowa
- Degree in
- Neuroscience
- Date degree season
- Spring 2025
- DOI
- 10.25820/etd.007842
- Publisher
- University of Iowa
- Number of pages
- xi, 125 pages
- Copyright
- Copyright 2025 Maya Evans
- Grant note
- TNJ was supported by the Andrew H. Woods Professorship and the Eagles Autism Foundation. TA was supported by Roy J. Carver Chair in Neuro- science, the University of Iowa Hawkeye Intellectual and Developmental Disabilities Research Center (Grant No. P50 HD 103556), and National Institute of Health (Grant No. R01 MH 087463). HES was supported by the Ida P. Haller Chair in Child Psychiatry and National Institute of Health (Grant No. R01 MH122485-03).
- Language
- English
- Date submitted
- 04/28/2025
- Description illustrations
- illustrations, graphs, tables
- Description bibliographic
- Includes bibliographical references (pages 95-116).
- Public Abstract (ETD)
- Severe stress experienced by a mother during pregnancy, also called prenatal stress, can be linked with the development of their baby’s brain. Studies show that prenatal stress increases risk for autism spectrum disorder (ASD) in children. However, we do not know exactly what leads to this increased risk. One brain region we are interested in investigating is the dorsal striatum, because it is impacted by prenatal stress, and many people with ASD show abnormalities here, especially enlargement. The dorsal striatum is important for the control of movement, procedural learning, and the estimation of time intervals. To examine the effects of prenatal disruptions on the dorsal striatum, we induced stress in pregnant mice. We found that prenatal stress changed the molecular makeup of dorsal striatal cells in offspring. It also impacted ASD-relevant behavior in the mouse offspring, improving procedural learning and altering their estimation of a time interval. By measuring electrical activity of neurons in the dorsal striatum, we observed abnormal activity patterns that likely underlie their changes in time estimation. To better understand the role of dorsal striatal enlargement in ASD, we artificially induced overgrowth of this brain region in mice. Findings indicated changes to postnatal development and adult behaviors linked to the dorsal striatum. Overall, we extended our understanding of how the dorsal striatum may be impacted by prenatal disruptions such as maternal stress, and how this may contribute to ASD-relevant behaviors. Results identified here may help to develop new prevention and treatment strategies for individuals with developmental disorders.
- Academic Unit
- Interdisciplinary Graduate Program in Neuroscience
- Record Identifier
- 9984831122902771
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