GluN2A- and GluN2B-containing pre-synaptic N -methyl- d -aspartate receptors differentially regulate action potential-evoked Ca 2+ influx via modulation of SK channels

• Published in: Philosophical transactions of the Royal Society of London. Series B. Biological sciences Vol. 379; no. 1906; p. 20230222
• Main Authors: Schmidt, Carla C., Tong, Rudi, Emptage, Nigel J.
• Format: Journal Article
• Language: English
• Published: England 29.07.2024
• Subjects: Action Potentials - physiology; Animals; Calcium - metabolism; Neuronal Plasticity - physiology; Pyramidal Cells - metabolism; Pyramidal Cells - physiology; Rats; Receptors, N-Methyl-D-Aspartate - metabolism; Small-Conductance Calcium-Activated Potassium Channels - metabolism; Synapses - metabolism; Synapses - physiology; homeostatic plasticity; NMDA receptor; pre-synaptic terminal; SK channel; short-term plasticity
• ISSN: 0962-8436; 1471-2970
• DOI: 10.1098/rstb.2023.0222

N -methyl- d -aspartate receptors (NMDARs) play a pivotal role in synaptic plasticity. While the functional role of post-synaptic NMDARs is well established, pre-synaptic NMDAR (pre-NMDAR) function is largely unexplored. Different pre-NMDAR subunit populations are documented at synapses, suggesting that subunit composition influences neuronal transmission. Here, we used electrophysiological recordings at Schaffer collateral-CA1 synapses partnered with Ca 2+ imaging and glutamate uncaging at boutons of CA3 pyramidal neurones to reveal two populations of pre-NMDARs that contain either the GluN2A or GluN2B subunit. Activation of the GluN2B population decreases action potential-evoked Ca 2+ influx via modulation of small-conductance Ca 2+ -activated K+ channels, while activation of the GluN2A population does the opposite. Critically, the level of functional expression of the subunits is subject to homeostatic regulation, bidirectionally affecting short-term facilitation, thus providing a capacity for a fine adjustment of information transfer. This article is part of a discussion meeting issue ‘Long-term potentiation: 50 years on’.