Review Article

NMDA Receptor Subunits Change after Synaptic Plasticity Induction and Learning and Memory Acquisition

Table 1

Changes in NMDAR subunits after plasticity induction. Changes in NMDAR expression or in NMDAR subunits level after inducing plasticity in several experimental models.

Animal model (age)Experimental protocolStructure analyzedMethodTimingNMDAR changesRef.

Adult Sprague-Dawley ratsLTP in vivo in the dentate gyrusDentate gyrusWB of whole homogenates0, 0.20, 1, 4, and 48 hs and 2 weeks after LTP inductionIncrease of GluNB and GluN2A at 20 and 48 hs after LTP induction.[28]
Sprague-Dawley rats (6–8 weeks)LTP induction in CA1 minislicesHippocampal CA1 region(i) WB of synaptosomal membrane and light membrane fractions from minislices30 min after LTP induction (subcellular fractionation assay)Enhanced surface expression of GluN1 and GluN2A at 30 min after stimulation, with a significant decrease in the intracellular pools. There is no change in total NMDAR level (both methods).[33]
(ii) WB of BS3-treated homogenates (cross-linking assay) from minislices0, 30, 60, 90, 120, 150, and 180 min (cross-linking assay)The increase of GluN1 and GluN2A starts at 15 min and persists for at least 3 h after LTP induction (cross-linking assay).
Rats (6-7 days)LTP induction in organotypic cultures of hippocampal slicesHippocampal CA1 regionWhole-cell recordingsGluN2A-NMDAR increase.[32]
Adult Sprague-Dawley ratsLTP in vivo in the dentate gyrusDentate gyrusWB of whole homogenates and synaptoneurosomes0.20, 4, 8, and 48 h and 2 weeks after LTP induction (whole homogenates assay)Increase of GluN1 at 8 and 48 h after LTP induction (whole homogenate assay).[29]
0.20 and 48 h (synaptoneurosomes assay)Increase of GluN2B at 0.20 and 48 h following LTP induction. Increase of GluN1 at 48 h, but not at 20 min, post LTP induction (synaptoneurosomes assay).
Sprague-Dawley rats (2 to 21 days)LTP induction in hippocampal slicesHippocampal CA1 regionNMDA EPSCs recordingsMilliseconds to secondsRapid synaptic shift from GluN2B-NMDAR to GluN2A-NMDAR in young, but not in adult, animals, after LTP induction.[31]
Adult Sprague-Dawley ratsLTP in vivo in the dentate gyrusDentate gyrusWB of synaptoneurosomes, biotin-tagged synaptic surface extracts and PSD fractions20 h and 2 weeks after LTP inductionIncrease of GluN1 in the surface-membrane fraction and synaptoneurosomes, but not in PSD fractions, at 48 h post LTP induction.
GluN1 levels in surface extracts returning to baseline at 2 weeks post stimulation.
[30]
Sprague-Dawley rat embryos (E18)Glycine stimulation in hippocampal neuron cultures (21–24 DIV)Hippocampus(i) WB of homogenates from biotinylated primary cultures
(ii) IF of primary cultures
30 min after glycine stimulationEnhanced surface expression of GluN1 and GluN2A after stimulation, without change in GluN2B.
Glycine also increased total GluN1 and GluN2A protein levels.
[37]
Sprague-Dawley rat embryos (E18)NMDA stimulation in hippocampal neuron cultures (21–24 DIV)Hippocampus(i) WB of homogenates from primary cultures
(ii) IF of primary cultures
From immediately 30 min after stimulationEnhanced surface expression of GluN1 and GluN2A after stimulation, without change in GluN2B.
NMDA also increased total GluN1 and GluN2A protein levels.
[36]
Wistar rats (P 42–60)LTP induction in hippocampal slicesHippocampusWB of whole-slice homogenates0, 30, and 70 min after LTP inductionIncrease of GluN1 and GluN2A, but not GluN2B, at 70 min after LTP induction.[34]