NMDAR LTP and LTD induction: 2B or Not 2B... is that the question?

Abstract

NMDA receptor (NMDAR) dependent forms of synaptic plasticity are thought to play critical roles in many aspects of CNS function and dysfunction, from learning and memory to addiction. NMDARs are heteromeric tetramers principally comprised of two NR1 subunits and two of four varieties of NR2 subunits (NR2A-2D). Recently, it has been proposed that specific NR2 subtypes subserve distinct roles in NMDAR-dependent long-term potentiation (LTP) and long-term depression (LTD). Here, we will review this literature, and describe an existing countervailing hypothesis, the charge-transfer hypothesis, which postulates that the total charge transfer through NMDARs, rather than specific subunits, dictates the polarity of synaptic plasticity. We will propose that a modification of the charge-transfer hypothesis, to include the possible involvement of protein-protein interactions imparted by distinct NR2 subunits, best fits the existing data. © Springer Verlag 2007.