The NMDA receptor subunit GluN3A protects against 3-nitroproprionic-induced striatal lesions via inhibition of calpain activation

► We tested the neuroprotective effects of genetic overexpression of GluN3A subunits. ► GluN3A protects vulnerable striatal medium-spiny neurons from excitotoxic damage. ► GluN3A-containing NMDARs in striatal neurons incorporate GluN1 and GluN2B subunits. ► GluN3A-containing NMDARs are targeted to synaptic and extrasynaptic compartments. ► GluN3A overexpression suppresses toxic calpain activation.