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

Abstract

It is widely accepted that NMDA receptors (NMDAR) are required for learning and memory formation, and for synaptic plasticity induction. We have previously shown that hippocampal GluN1 and GluN2A NMDAR subunits significantly increased following habituation of rats to an open field (OF), while GluN2B remained unchanged. Similar results were obtained after CA1-long-term potentiation (LTP) induction in rat hippocampal slices. Other studies have also shown NMDAR up regulation at earlier and later time points after LTP induction or learning acquisition. In this work, we have studied NMDAR subunits levels in the hippocampus and prefrontal cortex (PFC) after OF habituation and after object recognition (OR), to find out whether rising of NMDAR subunits is a general and structure-specific feature during memory formation. In 1, 2 and 3 month old rats there was an increase in hippocampal GluN1 and GluN2A, but not in GluN2B levels 70 min after OF habituation. This rise overlaps with early phase of memory consolidation, suggesting a putative relationship between them. The increases fell down to control levels 90 min after training. Similar results were obtained in the hippocampus of adult rats 70 min after OR training, without changes in PFC. Following OF test or OR discrimination phase, NMDAR subunits remained unchanged. Hence, rising of hippocampal GluN1 and GluN2A appears to be a general feature after novel “spatial/discrimination” memory acquisition. To start investigating the dynamics and possible mechanisms of these changes, we have studied hippocampal neuron cultures stimulated by KCl to induce plasticity. GluN1 and GluN2A increased both in dendrites and neuronal bodies, reaching a maximum 75 min later and returning to control levels at 90 min. Translation and/or transcription and mobilization differentially contribute to this rise in subunits in bodies and dendrites. Our results showed that the NMDAR subunits increase follows a similar time course both in vitro and in vivo. These changes happen in the hippocampus where a spatial representation of the environment is being formed making possible short term and long term memories (STM and LTM); appear to be structure-specific; are preserved along life; and could be related to synaptic tagging and/or to memory consolidation of new spatial/discrimination information.

PKMζ Inhibition Disrupts Reconsolidation and Erases Object Recognition Memory

“…The lack of effect of ZIP in ORM consolidation does not mean that the hippocampus does not participate in this process. Although it is true that, based mainly on lesion studies, it has previously been suggested that the involvement of the hippocampus in ORM is restricted to the processing of spatial and contextual information instead of recognition memory per se (Ainge et al, 2006), it has lately become clear that this region is critical for ORM consolidation even when all spatial and contextual compo-nents of the task are omitted (Liu et al, 2016;Stackman et al, 2016;Canto de Souza et al, 2017;Cercato et al, 2016;Lymer et al, 2017). This is particularly evident when rodents are exposed to two identical or two different but behaviorally equivalent objects in a familiar open-field arena.…”

Gadd45α modulates aversive learning through post‐transcriptional regulation of memory‐related mRNA s

“…Similar alterations were found for other Gadd45a-regulated targets, such as Grin2b (ionotropic glutamate receptor, subunit epsilon 2), Kcnq3 (potassium voltage-gated channel, subfamily Q, member 3), and Grm5 (metabotropic glutamate receptor 5) (Appendix Fig S3A-F). Of note, these genes have been previously implicated in memory formation and synaptic plasticity [28][29][30][31][32][33][34].…”

Synaptic GluN2A-Containing NMDA Receptors: From Physiology to Pathological Synaptic Plasticity

“…GluN2A-containing NMDARs are highly expressed in the adult hippocampus and neocortex while in other brain areas such as the striatum the GluN2B-containing NMDARs are predominant. Notably, GluN2A-containing NMDARs are more localized at synaptic sites and enriched in the postsynaptic density (PSD) compared to extrasynaptic sites [22][23][24] and display a slower mobility compared to other GluN2-containing ones [25].…”