NMDA receptor functions in health and disease: Old actor, new dimensions

Julien P. Dupuis, Olivier Nicole, Laurent Groc
Neuron. 2023-08-01; 111(15): 2312-2328
DOI: 10.1016/j.neuron.2023.05.002

Dupuis JP(1), Nicole O(1), Groc L(2).

Author information:
(1)University of Bordeaux, CNRS, IINS, UMR 5297, 33000 Bordeaux, France.
(2)University of Bordeaux, CNRS, IINS, UMR 5297, 33000 Bordeaux, France.
Electronic address: .

N-Methyl-D-aspartate ionotropic glutamate receptors (NMDARs) play key roles in
synaptogenesis, synaptic maturation, long-term plasticity, neuronal network
activity, and cognition. Mirroring this wide range of instrumental functions,
abnormalities in NMDAR-mediated signaling have been associated with numerous
neurological and psychiatric disorders. Thus, identifying the molecular
mechanisms underpinning the physiological and pathological contributions of
NMDAR has been a major area of investigation. Over the past decades, a large
body of literature has flourished, revealing that the physiology of ionotropic
glutamate receptors cannot be restricted to fluxing ions, and involves
additional facets controlling synaptic transmissions in health and disease.
Here, we review newly discovered dimensions of postsynaptic NMDAR signaling
supporting neural plasticity and cognition, such as the nanoscale organization
of NMDAR complexes, their activity-dependent redistributions, and non-ionotropic
signaling capacities. We also discuss how dysregulations of these processes may
directly contribute to NMDAR-dysfunction-related brain diseases.

DOI: 10.1016/j.neuron.2023.05.002
PMID: 37236178 [Indexed for MEDLINE]

Conflict of interest statement: Declaration of interests The authors declare no
competing interests.