Comment on "Role of NMDA Receptor Subtypes in Governing the Direction of Hippocampal Synaptic Plasticity"

Abstract

Taken together with recent evidence that extrasynaptic spillover of glutamate is detected exclusively by NR2B-containing NMDA receptors (7–9), these findings provide a novel mechanism for homeostatic regulation of excitatory transmission (10) and for sharpening pattern storage in the neuronal network. An elevation in ambient glutamate, released from multiple synapses and sensed by extrasynaptic NR2B-containing receptors, should trigger widespread LTD if accompanied by neuronal depolarization (Fig. 1). This does not preclude induction of LTP at synapses where glutamate is released and opens synaptic NR2A-containing receptors. The higher affinity of NR2B- than NR2A-containing receptors for glutamate (11) is well suited to their proposed role in weakening transmission as a function of heterosynaptic activity.