# Identification of bacterial products required for brain development

> **NIH NIH R21** · UNIVERSITY OF OREGON · 2020 · $184,375

## Abstract

There is mounting evidence that the intestinal microbiota play an important role in normal nervous system
development, although the underlying molecular mechanisms are generally unknown. We propose to
investigate the role of the intestinal microbiota in development of an identified population of superficial
interneurons (SINs) in the zebrafish optic tectum that are required for visually-guided prey capture behavior.
Previous work showed that prey capture is significantly impaired in larvae in which SINs are genetically
ablated. We find that the microbiota are necessary for SINs to differentiate their GABAergic phenotype, and
consequently larvae reared germ free (GF), in the absence of bacteria, phenocopy the prey capture deficit of
larvae in which SINs have been ablated. We hypothesize that members of the zebrafish-associated microbiota
normally produce molecular products that promote SIN differentiation. We will test this hypothesis using an
unbiased screen to identify bacterial products that affect SIN differentiation. First we will use gnotobiotic
zebrafish colonized with specific zebrafish bacterial isolates to learn which bacterial species are required for
normal SIN development and prey capture behavior. We will then take advantage of a pipeline we established
that utilizes bacterial genetics, bioinformatics, and biochemical approaches, to learn the molecular nature of
the bacterial products. Discovering the molecular mechanisms by which host-associated bacteria promote
normal nervous system development will provide important new insights into a fundamental process that is not
well understood, reveal how this process can go awry during intestinal dysbiosis, an imbalance that has been
linked to neurodevelopmental conditions such as autism spectrum disorder and schizophrenia, and provide
new possibilities for developing targeted therapies.

## Key facts

- **NIH application ID:** 9935120
- **Project number:** 5R21MH120427-02
- **Recipient organization:** UNIVERSITY OF OREGON
- **Principal Investigator:** JUDITH S EISEN
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $184,375
- **Award type:** 5
- **Project period:** 2019-06-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9935120

## Citation

> US National Institutes of Health, RePORTER application 9935120, Identification of bacterial products required for brain development (5R21MH120427-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9935120. Licensed CC0.

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