The role of NMDA receptors in memory and prediction in cultured neural networks

Memory has been extensively studied at the behavioural as well as the cellular level. Spike timing dependent plasticity (STDP) is associated with N-methyl-D-aspartate (NMDA) receptor activation and is widely accepted to be essential for long-term memory. However, experimental evidence remains sparse, probably due to the required complex combination of cellular and functional readouts. Recent work showed that in-vitro cortical networks memorize and predict inputs. The initial dependency of prediction on short-term memory decreased during the formation of long-term memory traces. Here, we stimulated in-vitro networks to investigate memory and prediction under control conditions, or under NMDA block. The NMDA anatagonist 2-amino-5-phosphonovaleric acid (APV) at a concentration that did not significantly reduce network excitability, but did impede long-term memory trace formation. In APV-treated cultures short-term memory of stimuli persisted, and they were still able to predict. In contrast to control cultures, prediction remained fully dependent on short-term memory. This confirms that NMDA receptor activation is essential for the formation of long-term memory traces and supports the notion that, as control cultures learn to memorize the stimulus, long-term memory starts to contribute to their predictive capability.