# Neural circuits underlying temporal integration of sounds and their dysregulation in an ASD model

> **NIH NIH F31** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2021 · $38,861

## Abstract

Project Summary
The brain’s ability to extract relevant information and filter out distractors from a complex sound environment is
critical to perceive physiologically relevant sounds such as language. This ability is often deficient in Autism
spectrum disorder (ASD) and affects the ability of patients to understand and interact with the world around
them. Specifically, ASD patients have reduced response to speech, hypersensitivity to normal stimuli, and are
easily overwhelmed in noisy environments. These sensory processing deficits could be attributed to changes in
the neuronal circuitry that affect how sounds are integrated to perceive relevant stimuli. In humans, integration
of individual sounds is dependent on the synchrony of the components’ onset within a 30-ms window, and
accurately integrating harmonic sounds in particular is critical for our perception of language. However, the
neuronal circuits that underlie complex sound integration in the auditory cortex and how they contribute to
sensory deficits in ASD are unclear. To address this gap in knowledge, I will identify the neuronal circuit
mechanisms underlying the temporal integration of harmonic sounds in the auditory cortex. In addition, I will
use a mouse model of Angelman syndrome (AS, Ube3am-/p+) to investigate how these circuits contribute to
sensory processing and speech discrimination deficits. I hypothesize that the temporal integration window
for binding of harmonic sounds, and thus the ability to integrate information originating from the same
source, is controlled by the activity of inhibitory neurons in cortical circuits. In addition, I expect that
an alteration of inhibition in AS mice changes the time window for integration of harmonic sounds,
which contributes to sensory processing deficits in ASD patients. In this proposal I aim to 1) Compare the
perceptual window of harmonics between wild-type (WT) and AS mice using a behavioral discrimination task,
2) Determine the neuronal mechanism of harmonics integration in WT and AS mice using in vivo two-photon
calcium imaging, and 3) Identify the culprits underlying AS phenotypes by rescuing Ube3a expression in
specific cell types. Overall, this study will contribute to our knowledge of how harmonic sounds are integrated
in the auditory cortex, which has valuable implications for our understanding of how we process speech. In
addition, identifying cell types that contribute to sensory processing deficits in neurodevelopmental disorders
could identify therapeutic targets to improve the lives of patients.

## Key facts

- **NIH application ID:** 10150535
- **Project number:** 5F31NS111849-03
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Amber M Kline
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $38,861
- **Award type:** 5
- **Project period:** 2019-05-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10150535

## Citation

> US National Institutes of Health, RePORTER application 10150535, Neural circuits underlying temporal integration of sounds and their dysregulation in an ASD model (5F31NS111849-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10150535. Licensed CC0.

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