# Mechanisms Shaping Temporal Integration in the Inferior Colliculus

> **NIH NIH F31** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2024 · $20,908

## Abstract

Abstract
Natural sounds contain rapid fluctuations in the amplitude envelope, and detecting these changes is an im-
portant task of the auditory system. Early auditory structures such as the cochlear nucleus primarily encode
amplitude modulations (AMs) in sound by phase locking their firing to the AM waveform, while the auditory cor-
tex primarily uses changes in firing rate to encode AM modulation frequencies. Located in the middle of the
ascending auditory pathway, the inferior colliculus (IC) plays a critical role in transforming the temporal code of
the periphery to the rate code that predominates in the thalamus and cortex. However, little is known about the
cellular mechanisms that underlie the shift from temporal to rate coding of AM stimuli in the IC. The overall ob-
jective of this proposal is to determine how NMDA receptors (NMDARs) contribute to the transition from tem-
poral to rate codes in the IC. NMDARs are glutamate receptors that are prominently expressed in the IC and
that prolong the time window for synaptic integration due to their slow kinetics compared to AMPA receptors.
These properties make NMDARs strong candidates for supporting a temporal to rate code transition. Con-
sistent with this, previous work showed that blocking NMDARs flattened firing rate AM tuning curves in the IC
while leaving temporal coding intact. Furthermore, while most NMDARs in the brain require depolarization to
relieve Mg2+ block, many IC neurons exhibit NMDAR responses at resting potential, which is expected to en-
hance their capacity to prolong the time window for synaptic integration. Our preliminary data provide the first
molecular mechanism for this phenomenon, showing that many IC neurons express NR2C or NR2D subunits,
NMDAR subunits which confer decreased sensitivity to Mg2+ block and enable NMDARs to activate at resting
membrane potential. We also found that NR2D subunits are expressed in VIP neurons, a recently identified
class of IC principal neurons, providing us a tool to reliably access a population of NR2D-expressing neurons.
Our preliminary data show that NR2D-containing NMDARs facilitate synaptic integration in VIP neurons in
vitro. We therefore hypothesize that NR2C/NR2D-containing NMDARs facilitate a shift from temporal to rate
coding in the IC by enhancing the time window for synaptic integration of phase-locked ascending inputs and
transforming those into a rate code. To test this hypothesis, in Aim 1 we will record in vitro from VIP neurons in
the IC and use optogenetics, pharmacology, and dynamic clamp experiments to determine how NR2D-contain-
ing NMDARs influence synaptic integration. In Aim 2, we will use pharmacology and in vivo recordings in
awake mice to test how rate coding for AM stimuli in the IC is shaped by NR2C/NR2D-containing NMDARs.
Overall, our results will reveal cellular mechanisms underlying the shift from temporal to rate coding in the IC,
which will help us better understand how AMs in sound are encoded in t...

## Key facts

- **NIH application ID:** 10836371
- **Project number:** 5F31DC021344-02
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Audrey Claire Drotos
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $20,908
- **Award type:** 5
- **Project period:** 2023-09-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10836371

## Citation

> US National Institutes of Health, RePORTER application 10836371, Mechanisms Shaping Temporal Integration in the Inferior Colliculus (5F31DC021344-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10836371. Licensed CC0.

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