Towards resolving the presynaptic NMDA receptor debate

Publication date: August 2018
Source:Current Opinion in Neurobiology, Volume 51
Author(s): Guy Bouvier, Rylan S Larsen, Antonio Rodríguez-Moreno, Ole Paulsen, P Jesper Sjöström
In the classical view, postsynaptic NMDA receptors (NMDARs) trigger Hebbian plasticity via Ca²⁺ influx. However, unconventional presynaptic NMDARs (preNMDARs) which regulate both long-term and short-term plasticity at several synapse types have also been found. A lack of sufficiently specific experimental manipulations and a poor understanding of how preNMDARs signal have contributed to long-standing controversy surrounding these receptors. Although several prior studies linked preNMDARs to neocortical timing-dependent long-term depression (tLTD), a recent study argues that the NMDARs are actually postsynaptic and signal metabotropically, that is, without Ca²⁺. Other recent work indicates that, whereas ionotropic preNMDARs signaling controls evoked release, spontaneous release is regulated by metabotropic NMDAR signaling. We argue that elucidating unconventional NMDAR signaling modes—both presynaptically and metabotropically—is key to resolving the preNMDAR debate.



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