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bioRxiv · 10.1101/2023.04.27.538607

GluN2D-containing NMDA receptors enhance temporal integration in VIP neurons in the inferior colliculus

Drotos, A. C.·Herrera, Y. N.·Zarb, R. L.·Roberts, M. T.
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Abstract

Along the ascending auditory pathway, there is a broad shift from temporal coding, which is common in the lower auditory brainstem, to rate coding, 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 Mg2+ block, and thus can conduct current at resting membrane potential. Using in situ hybridization and pharmacology, we show that VIP 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 VIP 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 (AM) 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. Significance statementNMDA 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 Mg2+ block than the more commonly expressed GluN2A/B subunits. We showed 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.

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Drotos, A. C., Herrera, Y. N., Zarb, R. L., Roberts, M. T.. 2023-04-27. GluN2D-containing NMDA receptors enhance temporal integration in VIP neurons in the inferior colliculus. https://doi.org/10.1101/2023.04.27.538607

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