# Synaptic, Cellular and Circuit Mechanisms of Cortical Plasticity after Cochlear Damage

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $619,224

## Abstract

PROJECT SUMMARY
In all sensory systems, peripheral sensory organ damage leads to compensatory cortical plasticity that supports
a remarkable recovery of perceptual capabilities. In the auditory system, while auditory nerve input to the
brainstem is significantly reduced after cochlear damage, sound-evoked cortical activity is maintained or even
enhanced. This recovery is due to increased cortical sensitivity (gain) to the spared auditory input. Although this
plasticity does not support features of sound processing encoded by the precise timing of neuronal firing, such
as complex sound discrimination, it provides a remarkable recovery of sound detection. A major gap in
knowledge is the lack of a precise mechanism that explains how this plasticity is implemented and distributed
over the diverse excitatory and inhibitory cortical neurons, synapses and circuits. Here we propose a strategic,
cooperative, time-dependent, cell type- and synapse-specific plasticity program that restores cortical sound
processing. The results from our studies will advance the field to a new level of understanding regarding cortical
plasticity after peripheral organ damage, and will inspire the development of well-timed, cell-specific treatments
and rehabilitative paradigms and cures that may further enhance the recovery of perception after hearing loss,
and mitigate the development of brain plasticity-related disorders, such as hyperacusis and tinnitus.
Cortical principal neurons (PN) and interneurons (IN) are very diverse and thus capable of supporting a
coordinated and collaborative plan for achieving cortical recovery. The major classes of cortical neurons include
vasoactive intestinal-peptide (VIP), somatostatin (SOM) and parvalbumin (PV) expressing IN sub-classes, as
well as intratelencephalic (IT), layer (L) 5 pyramidal tract (PT), and L6 corticothalamic (CT) PNs. Based on our
preliminary results, we propose that: 1) PVs are the network “stabilizers”; 2) VIPs are the “enablers” that regulate
SOM activity; and 3) SOMs are the “modulators” that allow for high PN gain. At the cellular and synaptic level,
we propose that soon after cochlear damage: 4) PVs and PTs exhibit a decrease in intrinsic excitability; 5) CTs
exhibit an increase in intrinsic excitability; and 6) thalamic synaptic input to deep cortical layers is shifted from
CT/PT equivalent to CT dominant. Overall, our proposed research and hypotheses provide an experimental
platform to probe how multiple cortical neuronal sub-classes restore cortical processing after peripheral input
loss (Aims 1 and 3). In combination with Aims 2 and 3, our proposed studies will determine the underlying intrinsic
(Aim 2) and synaptic mechanisms (Aim 3) that mediate this plasticity.

## Key facts

- **NIH application ID:** 10273218
- **Project number:** 1R01DC019618-01
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Thanos Tzounopoulos
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $619,224
- **Award type:** 1
- **Project period:** 2021-06-03 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10273218

## Citation

> US National Institutes of Health, RePORTER application 10273218, Synaptic, Cellular and Circuit Mechanisms of Cortical Plasticity after Cochlear Damage (1R01DC019618-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10273218. Licensed CC0.

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