Functional contributions of synaptically localized NR2B subunits of the NMDA receptor to synaptic transmission and long‐term potentiation in the adult mouse CNS

Abstract

The NMDA-type glutamate receptor is a heteromeric complex composed of the NR1 and at least one of the NR2 subunits. Switching from the NR2B to the NR2A subunit is thought to underlie functional alteration of the NMDA receptor during synaptic maturation, and it is generally believed that it results in preferential localization of NR2A subunits on the synaptic site and that of NR2B subunits on the extracellular site in the mature brain. It has also been proposed that activation of the NR2A and NR2B subunits results in long-term potentiation (LTP) and long-term depression (LTD), respectively. Furthermore, recent reports suggest that synaptic and extrasynaptic receptors may have distinct roles in synaptic plasticity as well as in gene expression associated with neuronal death. Here, we have investigated whether NR2B subunit-containing receptors are present and functional at mature synapses in the lateral nucleus of the amygdala (LA) and the CA1 region of the hippocampus, comparing their properties between the two brain regions. We have found, in contrast to the above hypotheses, that the NR2B subunit significantly contributes to synaptic transmission as well as LTP induction. Furthermore, its contribution is greater in the LA than in the CA1 region, and biophysical properties of NMDA receptors and the NR2B/NR2A ratio are different between the two brain regions. These results indicate that NR2B subunit-containing NMDA receptors accumulate on the synaptic site and are responsible for the unique properties of synaptic function and plasticity in the amygdala.

Involvement of the GluN2A and GluN2B Subunits in Synaptic and Extrasynaptic N-methyl-d-aspartate Receptor Function and Neuronal Excitotoxicity

“…GluN2A-and GluN2B-containing NMDARs differ in channel kinetics, open probability, ligand affinity, and the interaction with intracellular signaling and scaffold proteins (14). Previous studies have demonstrated that GluN2A and GluN2B are expressed predominantly at the synapse and extrasynaptic locations, respectively (12,13,45,46). Functionally, GluN2A-containing NMDARs mediated roughly 68% of the synaptic current and 27% of the extrasynaptic current.…”

Effects of Elevation of Brain Magnesium on Fear Conditioning, Fear Extinction, and Synaptic Plasticity in the Infralimbic Prefrontal Cortex and Lateral Amygdala

“…7 A, C) under physiological [Mg 2ϩ ] o conditions (0.8 mM). Furthermore, the portion of NR2B-containing NMDAR current is ϳ40% in the lateral amygdala, 20% in hippocampus (Miwa et al, 2008), and ϳ15% in the PFC synapses (Zhao et al, 2005). Electron microscopy studies show that NMDARs at synapses in the lateral amygdala contain larger number of NR2B subunits than synapses in the hippocampal CA1 (Miwa et al, 2008).…”

“…Furthermore, the portion of NR2B-containing NMDAR current is ϳ40% in the lateral amygdala, 20% in hippocampus (Miwa et al, 2008), and ϳ15% in the PFC synapses (Zhao et al, 2005). Electron microscopy studies show that NMDARs at synapses in the lateral amygdala contain larger number of NR2B subunits than synapses in the hippocampal CA1 (Miwa et al, 2008). Since the degree of LTP is strongly correlated with the size of the synaptic NMDA current, the above data might also explain why the LTP magnitude in the lateral amygdala synapses is higher than that in the IL-PFC under control conditions (Figs.…”

“…In this scenario, the sensitivity of NMDAR current to variations in [Mg 2ϩ ] o is the key for the magnesium-induced effects. Interestingly, the synaptic NMDAR current in thalamic-amygdala synapses are strongly blocked by physiological [Mg 2ϩ ] o such that elevation of [Mg 2ϩ ] o has little influence on synaptic NMDAR current near resting membrane potentials (Weisskopf and LeDoux, 1999;Miwa et al, 2008). If the homeostatic regulation of synaptic NMDARs by [Mg 2ϩ ] o is applicable to the lateral amygdala synapses, then one might predict that lateral amygdala synapses have higher synaptic NMDAR current and should have higher NR2B-containing NMDARs under physiological [Mg 2ϩ ] o .…”

Propofol exposure during early gestation impairs learning and memory in rat offspring by inhibiting the acetylation of histone

“…NR2B is an important positive regulator of learning and memory by promoting synaptic plasticity and LTP 16, 17. The balance between positive and negative learning and memory‐regulating genes and proteins is key to the formation, maintenance, as well as retrieval of memory.…”