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

Abstract

NMDA ionotropic glutamate receptors (NMDARs) are crucial in activity-dependent synaptic changes and in learning and memory. NMDARs are composed of two GluN1 essential subunits and two regulatory subunits which define their pharmacological and physiological profile. In CNS structures involved in cognitive functions as the hippocampus and prefrontal cortex, GluN2A and GluN2B are major regulatory subunits; their expression is dynamic and tightly regulated, but little is known about specific changes after plasticity induction or memory acquisition. Data strongly suggest that following appropriate stimulation, there is a rapid increase in surface GluN2A-NMDAR at the postsynapses, attributed to lateral receptor mobilization from adjacent locations. Whenever synaptic plasticity is induced or memory is consolidated, more GluN2A-NMDARs are assembled likely using GluN2A from a local translation and GluN1 from local ER. Later on, NMDARs are mobilized from other pools, and there are de novo syntheses at the neuron soma. Changes in GluN1 or NMDAR levels induced by synaptic plasticity and by spatial memory formation seem to occur in different waves of NMDAR transport/expression/degradation, with a net increase at the postsynaptic side and a rise in expression at both the spine and neuronal soma. This review aims to put together that information and the proposed hypotheses.

Figure 1

Schematic representation of the proposed model for NMDAR localization and expression after plasticity induction. After a stimulus that would elicit long-term plasticity, there is a rapid increase in surface GluN2A-NMDAR at the postsynaptic side, which is likely due to lateral receptor mobilization from adjacent locations (step 1). Whenever plasticity was effectively induced, more GluN2A-NMDARs would be assembled using GluN2A from local translation and GluN1 retained in local ER (step 2). As more NMDARs are needed, mobilization from other pools would contribute to enhance NMDAR expression at synapses (step 3). As nonsynaptic pools decrease, some signals should activate NMDAR subunits expression at the neuronal soma, which would lead to a transient increase in subunits level there (steps 4-5).