The Journal of physiologySep 6, 2024

Specific NMDA receptors increase sound responses and signal buildup in the brain's hearing center

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Updated Apr 2, 2026

Abstract

Blocking GluN2C/D-containing NMDA receptors decreases spontaneous and sound-evoked firing rates in many inferior colliculus neurons.

GluN2C and GluN2D mRNA are widely expressed in inferior colliculus neurons.
GluN2C/D-containing NMDA receptors can conduct current at resting membrane potential due to their insensitivity to voltage-dependent magnesium blockade.
These receptors have slower kinetics compared to other NMDA receptor subtypes, which enhances temporal summation of synaptic inputs.
In a model neuron, GluN2C/D-like conductance alters how neurons process temporal and rate information from auditory stimuli.
Blocking these receptors in vivo reduces both spontaneous firing rates and firing rates in response to amplitude-modulated sounds.

Simplified

Along the ascending auditory pathway, there is a broad shift from , which is common in the lower auditory brainstem, to , which predominates in auditory cortex. This temporal-to-rate transition is particularly prominent in the inferior colliculus (IC), the midbrain hub of the auditory system, but the mechanisms that govern how individual IC neurons integrate information across time remain largely unknown. Here, we report the widespread expression of Glun2c and Glun2d mRNA in IC neurons. GluN2C/D-containing NMDA receptors are relatively insensitive to voltage-dependent Mgblockade, and thus can conduct current at resting membrane potential. Using in situ hybridization and pharmacology, we show that vasoactive intestinal peptide neurons in the IC express GluN2D-containing NMDA receptors that are activatable by commissural inputs from the contralateral IC. In addition, GluN2C/D-containing receptors have much slower kinetics than other NMDA receptors, and we found that GluN2D-containing receptors facilitate temporal summation of synaptic inputs in vasoactive intestinal peptide neurons. In a model neuron, we show that a GluN2C/D-like conductance interacts with the passive membrane properties of the neuron to alter temporal and rate coding of stimulus trains. Consistent with this, we show in vivo that blocking GluN2C/D-containing receptors decreases both the spontaneous firing rate and the overall firing rate elicited by amplitude-modulated sounds in many IC neurons. These results suggest that GluN2C/D-containing NMDA receptors influence rate coding for auditory stimuli in the IC by facilitating the temporal integration of synaptic inputs. KEY POINTS: NMDA receptors are critical components of most glutamatergic circuits in the brain, and the diversity of NMDA receptor subtypes yields receptors with a variety of functions. We found that many neurons in the auditory midbrain express GluN2C and/or GluN2D NMDA receptor subunits, which are less sensitive to Mgblockade than the more commonly expressed GluN2A/B subunits. We show that GluN2C/D-containing receptors conducted current at resting membrane potential and enhanced temporal summation of synaptic inputs. In a model, we show that GluN2C/D-containing receptors provide additive gain for input-output functions driven by trains of synaptic inputs. In line with this, we found that blocking GluN2C/D-containing NMDA receptors in vivo decreased both spontaneous firing rates and firing evoked by amplitude-modulated sounds. 2+ 2+

Key numbers

91.4%

Percentage of expressing GluN2D

High expression of GluN2D in in the .

−3.03 Hz

Decrease in spontaneous firing rate after GluN2C/D blockade

Change in spontaneous firing rate during periods between stimulus presentations.

−1.11 Hz

Decrease in sound-evoked firing rate after GluN2C/D blockade

Change in firing rate during amplitude-modulated sound presentations.

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Specific NMDA receptors increase sound responses and signal buildup in the brain's hearing center

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