The GluN2A Subunit Regulates Neuronal NMDA receptor-Induced Microglia-Neuron Physical Interactions

Ukpong B. Eyo, Ashley Bispo, Junting Liu, Sruchika Sabu, Rong Wu, Victoria L. Dibona, Jiaying Zheng, Madhuvika Murugan, Huaye Zhang, Yamei Tang, LongJun Wu

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8 Scopus citations

Abstract

Microglia are known to engage in physical interactions with neurons. However, our understanding of the detailed mechanistic regulation of microglia-neuron interactions is incomplete. Here, using high resolution two photon imaging, we investigated the regulation of NMDA receptor-induced microglia-neuron physical interactions. We found that the GluN2A inhibitor NVPAAM007, but not the GluN2B inhibitor ifenprodil, blocked the occurrence of these interactions. Consistent with the well-known developmental regulation of the GluN2A subunit, these interactions are absent in neonatal tissues. Furthermore, consistent with a preferential synaptic localization of GluN2A subunits, there is a differential sensitivity of their occurrence between denser (stratum radiatum) and less dense (stratum pyramidale) synaptic sub-regions of the CA1. Finally, consistent with differentially expressed GluN2A subunits in the CA1 and DG areas of the hippocampus, these interactions could not be elicited in the DG despite robust microglial chemotactic capabilities. Together, these results enhance our understanding of the mechanistic regulation of NMDA receptor-dependent microglia-neuronal physical interactions phenomena by the GluN2A subunit that may be relevant in the mammalian brain during heightened glutamatergic neurotransmission such as epilepsy and ischemic stroke.

Original languageEnglish (US)
Article number828
JournalScientific Reports
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2018

ASJC Scopus subject areas

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    Eyo, U. B., Bispo, A., Liu, J., Sabu, S., Wu, R., Dibona, V. L., Zheng, J., Murugan, M., Zhang, H., Tang, Y., & Wu, L. (2018). The GluN2A Subunit Regulates Neuronal NMDA receptor-Induced Microglia-Neuron Physical Interactions. Scientific Reports, 8(1), [828]. https://doi.org/10.1038/s41598-018-19205-4