Closed head injury also resulted in transient decreases in GluN2A
and GluN2B subunits of the NMDA receptor.
Metaplasticity gated through differential regulation of GluN2A
versus GluN2B receptors by Src family kinases.
and GluN2B subunits have both been associated with LTP and cognitive function , and this is thought to be due to downstream activation of ERK .
In addition, NL1 KO mice showed significantly reduced expression levels of NMDA receptor subunits GluN1, GluN2A
, GluN2B and the AMPA receptor subunit GluA2 in synaptosomal hippocampal preparations .
At the time, NMDAR-dependent LTP was thought to require signaling via the GluN2A
receptor subunit (Liu et al.
Phillips, "NMDA GluN2A
and GluN2B receptors play separate roles in the induction of LTP and LTD in the amygdala and in the acquisition and extinction of conditioned fear," Neuropharmacology, vol.
During postnatal development of forebrain synapses, NMDARs transform from containing GluN2B to GluN2A
In CNS regions involved in cognitive functions, like the hippocampus and prefrontal cortex (PFC), GluN2A
and GluN2B are the major regulatory subunits [5, 13].
Unlike the majority of GPCRs, which are palmitoylated on one or two conserved cysteine residues within the C-terminal domain, palmitoylation of NMDARs takes place at two distinct cysteine clusters within the long intracellular C-terminal domain of GluN2A
and GluN2B receptor subunits [4, 176].
Consistently, the level of NMDA receptors (NMDARs), particularly GluN1 and GluN2A
subunits, is selectively reduced in the postsynaptic density (PSD) fraction of 14-3-3 FKO mice that exhibit deficits in cognitive behaviors and hippocampal LTP .
NMDARs are composed of the mandatory GluN1 subunit and a variety of GluN2A
, B, C, and D subunits [38, 40].