NMDA Receptor Subunits in the Adult Rat Hippocampus Undergo Similar Changes after 5 Minutes in an Open Field and after LTP Induction

Abstract

NMDA receptor subunits change during development and their synaptic expression is modified rapidly after synaptic plasticity induction in hippocampal slices. However, there is scarce information on subunits expression after synaptic plasticity induction or memory acquisition, particularly in adults. GluN1, GluN2A and GluN2B NMDA receptor subunits were assessed by western blot in 1) adult rats that had explored an open field (OF) for 5 minutes, a time sufficient to induce habituation, 2) mature rat hippocampal neuron cultures depolarized by KCl and 3) hippocampal slices from adult rats where long term potentiation (LTP) was induced by theta-burst stimulation (TBS). GluN1 and GluN2A, though not GluN2B, were significantly higher 70 minutes –but not 30 minutes- after a 5 minutes session in an OF. GluN1 and GluN2A total immunofluorescence and puncta in neurites increased in cultures, as evaluated 70 minutes after KCl stimulation. Similar changes were found in hippocampal slices 70 minutes after LTP induction. To start to explore underlying mechanisms, hippocampal slices were treated either with cycloheximide (a translation inhibitor) or actinomycin D (a transcription inhibitor) during electrophysiological assays. It was corroborated that translation was necessary for LTP induction and expression. The rise in GluN1 depends on transcription and translation, while the increase in GluN2A appears to mainly depend on translation, though a contribution of some remaining transcriptional activity during actinomycin D treatment could not be rouled out. LTP effective induction was required for the subunits to increase. Although in the three models same subunits suffered modifications in the same direction, within an apparently similar temporal course, further investigation is required to reveal if they are related processes and to find out whether they are causally related with synaptic plasticity, learning and memory.

Changes in synaptic transmission and protein expression in the brains of adult offspring after prenatal inhibition of the kynurenine pathway

“…Since the ratio between GluN2A and GluN2B subunits is known to change during the course of early brain development and to have a major influence on behavioral and electrophysiological outcomes by adulthood (Traynelis et al, 2010), the shifts we have reported in these two subunits may be among the more important factors in generating the functional synaptic changes described above. As noted earlier, the reduced LTP and GluN2A expression seen here is entirely compatible with the recently reported increase in expression of GluN2A induced by LTP (Baez et al, 2013).…”

Surface expression of NMDA receptor changes during memory consolidation in the crabNeohelice granulata

“…3). This led us to the idea that the regulation of the receptor was not at the protein expression level as seen in other memory models (Baez et al 2013) but rather at the surface expression level. The regulation at the surface expression level has been repeatedly reported in memory and synaptic plasticity experiments (Cammarota et al 2000;Grosshans et al 2002b;Moyano et al 2004;Mukherjee et al 2014).…”

GluN1 and GluN2A NMDA Receptor Subunits Increase in the Hippocampus during Memory Consolidation in the Rat

“…Therefore, this rise would take place during early memory consolidation phase and likely, during the establishment of an “effective” long-term synaptic plasticity (Baez et al, 2013). …”