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

Objective: Memory has been extensively studied at the behavioural as well as the cellular level. Spike timing dependent plasticity is widely considered essential for long-term memory and is associated with activation of N-methyl-D-aspartate (NMDA) receptors. This suggests that NMDA receptor activation plays a crucial role in enabling long-term memory. However, experimental evidence remains sparse, probably due to the complex combination of cellular and functional readouts required.

Approach: 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 networks of dissociated cortical neurons that were grown on multi electrode arrays to investigate memory and prediction under control conditions, or under NMDA block.

Main results: The NMDA antagonist 2-amino-5-phosphonovaleric acid (APV) at the used concentration impeded long-term memory trace formation, but did not significantly reduce network excitability. 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. Significance. 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.