# Elucidating neural substrates that mediate autism-like behaviors

> **NIH NIH R01** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2021 · $514,379

## Abstract

ABSTRACT
Developing fetus in maternal womb can be exposed to environmental stress, and this may lead
to the development of long-lasting neurological and behavioral changes. Uncontrolled
Inflammation encountered in utero and its effects on behaviors of offspring have been modeled
in rodents and subsequently coined as maternal immune activation (MIA). However, it is still
unknown how the immune activation, which takes place in pregnant dams, is translated into
neurological and behavioral changes in offspring.
Using both genetic mutants lacking a particular subset of pro-inflammatory immune cells and
blocking antibodies targeting their activities, we have recently found that pro-inflammatory T
helper cells (Th17 cells) expressing intereukin-17a (IL-17a) in mothers induce MIA-dependent
behavioral changes and abnormal cortical phenotypes in offspring. We also observed that the
receptor for IL-17a (IL-17Ra) is expressed in the fetal brain and its expression is increased in
the cortical plate upon MIA. These observations taken together suggest an exciting
hypothesis that uncontrolled activation of IL-17Ra expressed in fetal brain induces
abnormal cortical patches and these structural abnormalities eventually lead to the MIA-
associated behavioral phenotypes. Thus, in this application, we propose 1) to determine if
cortical abnormalities could predict behavioral phenotypes in MIA offspring, 2) to characterize
cortical abnormalities in adult MIA offspring, and 3) functionally determine if the cortical
phenotype is the underlying cause of the MIA behavioral abnormalities.

## Key facts

- **NIH application ID:** 10215438
- **Project number:** 5R01MH115037-05
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Gloria Choi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $514,379
- **Award type:** 5
- **Project period:** 2017-09-12 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10215438

## Citation

> US National Institutes of Health, RePORTER application 10215438, Elucidating neural substrates that mediate autism-like behaviors (5R01MH115037-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10215438. Licensed CC0.

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