Voltage-independent GluN2A-type NMDA receptor Ca²⁺ signaling promotes audiogenic seizures, attentional and cognitive deficits in mice.

ABSTRACT: The NMDA receptor-mediated Ca²⁺ signaling during simultaneous pre- and postsynaptic activity is critically involved in synaptic plasticity and thus has a key role in the nervous system. In GRIN2-variant patients alterations of this coincidence detection provoked complex clinical phenotypes, ranging from reduced muscle strength to epileptic seizures and intellectual disability. By using our gene-targeted mouse line (Grin2a^N615S), we show that voltage-independent glutamate-gated signaling of GluN2A-containing NMDA receptors is associated with NMDAR-dependent audiogenic seizures due to hyperexcitable midbrain circuits. In contrast, the NMDAR antagonist MK-801-induced c-Fos expression is reduced in the hippocampus. Likewise, the synchronization of theta- and gamma oscilla

SUBMITTER: Bertocchi I 

PROVIDER: S-EPMC7794508 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature