# NEURONAL CIRCUITS AND PLASTICITY OF NEONATAL AUDITORY CORTEX

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2024 · $619,297

## Abstract

Project Summary
Normal auditory cortex (ACX) function is crucial for speech and language perception. Many disorders that
involve ACX, such as Central Auditory Processing Disorders (CAPD), Autism Spectrum Disorder (ASD), and
tinnitus are thought to be due to abnormal brain wiring. Moreover, influences on the developing brain interact
with each other, e.g., early trauma or drug exposure can alter early sensory processing, resulting in wiring
deficits. Thus, correcting disorders would seem to require the ability to rewire the brain. An understanding of
brain development and the emergence of sensory function is needed to do so.
 Sensory experience, especially during early “critical periods,” sculpts connections in the young brain,
leading to altered functional responses and functional representation of sensory stimuli, e.g., sounds in the
brain. Manipulation or replacement of sensory experience (e.g., by cochlear implants) after the critical period
does not lead to successful functional recovery. We recently discovered that sensory experience, even before
the traditional “critical period,” can alter circuits associated with subplate neurons in the developing cortex.
Thus, sensory experience in this “pre-critical period,” which in humans occurs in utero, might fundamentally
shape ACX organization and sound processing, as well as influence mechanisms during the later “classic
critical period” within layer 4.
 We have shown that the earliest sound-responsive neurons in ACX are located in the subplate, an
enigmatic, deep cortical layer. Subplate neurons (SPNs) are mainly absent in adults, highlighting their
developmental role. SPNs are more numerous in primates than in other species. Thus, some SPNs may be an
evolutionary addition enabling complex brain function. Lesioning SPNs in visual and somatosensory cortex
alters cortical development, thus SPNs seem essential to development. We have found that ACX SPNs
receive thalamic inputs and project to cortical layer 4 before the onset of low-threshold hearing. Moreover, our
recent work established that SPN circuits are disrupted in deafness, and neurodevelopmental disorders.
However, a role for SPN activity in the development of ACX has yet to be established.
 As a step towards promoting functional recovery from early sensory disruptions or injury, we will investigate
i) how sound stimuli are processed by SPNs; iii) how dysfunction of specific SPN circuits leads to altered ACX
wiring; and iii) how SPNs modulate both spontaneous and sound-evoked cortical activity. To achieve our aims,
we will utilize state-of-the-art in vivo imaging and stimulation techniques.
 Our studies will elucidate processes underlying ACX development and contribute to understanding the
pathophysiology of many disorders, e.g., deafness, CAPD, ASD, and language impairments. Moreover, our
work will inform new treatments and how existing treatments must be modified to consider these changes.
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## Key facts

- **NIH application ID:** 10808652
- **Project number:** 2R01DC009607-17
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** PATRICK O KANOLD
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $619,297
- **Award type:** 2
- **Project period:** 2009-04-01 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10808652

## Citation

> US National Institutes of Health, RePORTER application 10808652, NEURONAL CIRCUITS AND PLASTICITY OF NEONATAL AUDITORY CORTEX (2R01DC009607-17). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10808652. Licensed CC0.

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