Multiple roles of GluN2D-containing NMDA receptors in short-term potentiation and long-term potentiation in mouse hippocampal slices

Abstract

The GluN2 subunits of N-methyl- d -aspartate receptors (NMDARs) are key drivers of synaptic plasticity in the brain, where the particular GluN2 composition endows the NMDAR complex with distinct pharmacological and physiological properties. Compared to GluN2A and GluN2B subunits, far less is known about the role of the GluN2D subunit in synaptic plasticity. In this study, we have used a GluN2C/2D selective competitive antagonist, UBP145, in combination with a GluN2D global knockout (GluN2D KO) mouse line to study the contribution of GluN2D-containing NMDARs to short-term potentiation (STP) and long-term potentiation (LTP) in the CA1 region of mouse hippocampal slices. We made several distinct observations: First, GluN2D KO mice have higher levels of LTP compared to wild-type (WT) mice, an effect that was occluded by blockade of GABA receptor-mediated inhibition or by using a strong LTP induction protocol. Second, UBP145 partially inhibited LTP in WT but not GluN2D KO mice. Third, UBP145 inhibited a component of STP, termed STP2, in WT but not GluN2D KO mice. Taken together, these findings suggest an involvement for GluN2D-containing NMDARs in both STP and LTP in mouse hippocampus.

Differential regulation of STP, LTP and LTD by structurally diverse NMDA receptor subunit-specific positive allosteric modulators

“…Similar to actions on LTD, 10 μM of UBP145 had no effect on the induction of LTP in either P14 ( France et al, 2017 ) or adult ( Volianskis et al, 2013a ) rat hippocampal slices, although partial inhibition of LTP has recently been described in adult mouse hippocampal slices ( Eapen et al, 2021 ; current issue). In both species, UBP145 inhibited the induction of a slow-decaying component of STP, termed STP2 ( Volianskis et al, 2013a ; France et al, 2017 ; Eapen et al, 2021 ). The fast-decaying component of STP that is not sensitive to inhibition by UPB145 is termed STP1 ( Fig.…”

Regulation and bioinformatic analysis of circ_0015891/miR-129-1-3p axis in methamphetamine-induced dopaminergic apoptosis

“…The other significantly DEG that enriched in amphetamine addiction pathway is GRIN2D, one of the 4 NMDAR2 (GRIN2) subunits. NMDARs are a species of ionotropic glutamate receptors controlled the opening and closing of NMDA channel which has been confirmed to be involved in long-term potentiation, an activity-dependent increase in the efficiency of synaptic transmission considered to regulate learning and memory ( 45 ). GRIN2D is a ligand-gated ion channel with high calcium permeability that causes intracellular calcium overload in pathological states contributing to induce developmental and epileptic encephalopathies ( 46 ).…”

Function of Excitatory Periaqueductal Gray Synapses in the Ventral Tegmental Area following Inflammatory Injury

“…Changes in Mg 2+ block and Ca 2+ entry will directly affect glutamatergic cellular communication. In the hippocampus, Glun2D subunits contribute to synapse maturation ( Yamasaki et al, 2014 ) and the expression of some forms of plasticity as pharmacological antagonism can reduce the magnitude of short-term potentiation or LTP depending on the stimulation protocol ( France et al, 2017 ; Eapen et al, 2021 ). However, how these manifest in the midbrain are unknown.…”