# Plastic Synaptic Interconnections between Principal cells of the Ventral Cochlear Nucleus

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2022 · $448,035

## Abstract

Project Summary
T Stellate cells of the ventral cochlear nucleus (VCN) form an important ascending pathway that transmits
spectral information from the auditory nerve to numerous auditory nuclei. They innervate the olivocochlear
efferents in the ventral nucleus of the trapezoid body, the lateral superior olive, the inferior colliculi and the
thalamus. In preliminary experiments we have discovered that groups of T stellate cells within an isofrequency
lamina are bidirectionally interconnected through excitatory synaptic connections that can be potentiated. In
dual, whole-cell patch-clamp recordings from T stellate cells, firing in a presynaptic cell generally evoked no
EPSCs in the postsynaptic cell unless presynaptic firing was paired with postsynaptic depolarization. These
findings are exciting for two reasons. First is that the mechanism underlying that potentiation is new and
unprecedented. Postsynaptic depolarization increased the probability of recorded EPSCs, a presynaptic
function, implicating the involvement of a retrograde messenger. Our preliminary results support the hypothesis
that nitric oxide serves as that retrograde signal. Aim 1 is to use intracellular recordings in slices to gain a
deeper understanding of the mechanisms that underlie potentiation of connections between T stellate cells and
to understand their source and dynamics. We will identify what neurons participate in polysynaptic
connections, how synaptic excitation by auditory nerve fibers affects the plasticity of interconnections, examine
signaling through the nitric oxide pathway, and measure rates at which potentiation develop and fade. Second
is that our discovery reveals a new form of central gain control at the network level. Bidirectional, excitatory
interconnections indicate that T stellate cells in an isofrequency lamina form a network and could explain how
T stellate cells can sharpen the encoding of spectral peaks. These interconnections could also form synaptic
positive feedback loops that lead to hyperexcitability in the face of loss of auditory nerve fibers and the
consequent uncoupling of excitation and inhibition. Aim 2 is to use computational neural models to understand
the implications of excitatory interconnections between T stellate cells on their encoding of sound. We will
implement models that can simulate the response features of single T stellate cells and build an interconnected
neural network to understand how network connectivity contributes to potentiation. We will test the hypothesis
that excitatory interconnections enhance the encoding of spectral peaks and that inhibition is required to
stabilize the network.

## Key facts

- **NIH application ID:** 10415856
- **Project number:** 5R01DC016861-05
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** PHILIP H SMITH
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $448,035
- **Award type:** 5
- **Project period:** 2018-03-15 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10415856

## Citation

> US National Institutes of Health, RePORTER application 10415856, Plastic Synaptic Interconnections between Principal cells of the Ventral Cochlear Nucleus (5R01DC016861-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10415856. Licensed CC0.

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