# Genetic and circuit control of visuo-acoustic behavior and integration

> **NIH NIH R15** · HAVERFORD COLLEGE · 2022 · $419,669

## Abstract

Function-disrupting AP2S1 alleles have recently been linked to learning disabilities and autism spectrum
disorders (ASD), though the mechanisms underlying this gene’s impact on human behavior are unknown.
Understanding how, when, and where this gene regulates vertebrate behavior is key to addressing deficits
observed in these and other neuropsychiatric conditions, yet viable vertebrate models are lacking. Our lab has
isolated viable zebrafish ap2s1 mutants and has begun to characterize AP2S1’s role in cognitive processes such
as integrating multisensory information, appropriate selection of behaviors, and habituation learning. Given that
deficits in information processing and behavioral selection are characteristics shared by many neuropsychiatric
conditions, including ASD and schizophrenia, our genetically-accessible model can be leveraged to determine
the molecular and neural mechanisms underlying these conditions as well as more broadly characterize ap2s1’s
role in multisensory integration, behavior selection, and learning.
 We will use our zebrafish model to reveal the neural mechanisms by which ap2s1 modulates visual and
acoustic behavior and sensory integration. In Aim 1, we will determine what aspects of visually guided learning,
visual behavior selection, and visuo-acoustic integration require ap2s1. Our results will test the hypothesis that
ap2s1 directly modulates visual processing and visuo-acoustic integration, beyond its role in acoustic behavior.
In Aim 2, we will determine the temporal and spatial requirements for ap2s1 to modulate visually and acoustically
evoked behavior using inducible and cell-specific transgenes. Our results will test the hypotheses that the
behavioral role of ap2s1 is 1) to regulate appropriate circuit development, and/or 2) to regulate acute neuronal
function, and will distinguish if ap2s1 regulates visual and acoustic responses through distinct or shared circuits.
In Aim 3, we will focus on the pair of command-like Mauthner neurons that integrate visual and acoustic
information to drive escape behavior, and determine how its function is modulated by ap2s1. Through subcellular
calcium imaging in behaving fish, our results will test the hypothesis that ap2s1 modulates escape behavior
selection through a spatially-specific impact on Mauthner dendritic integration, revealing the dynamics of visual
and acoustic information integration in these central neurons. Overall, these Aims will positively impact human
health initiatives by advancing our knowledge of the genetic and neural mechanisms governing multisensory
information processing and behavioral selection, and the direct roles of the ASD-linked gene AP2S1.
Furthermore, our proposed work will validate the use of these behavioral assays as a zebrafish model for
vertebrate multisensory integration that will be used to characterize other genes as they become clinically relevant.

## Key facts

- **NIH application ID:** 10439217
- **Project number:** 1R15EY031539-01A1
- **Recipient organization:** HAVERFORD COLLEGE
- **Principal Investigator:** Roshan A Jain
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $419,669
- **Award type:** 1
- **Project period:** 2022-09-30 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10439217

## Citation

> US National Institutes of Health, RePORTER application 10439217, Genetic and circuit control of visuo-acoustic behavior and integration (1R15EY031539-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10439217. Licensed CC0.

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