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

Abstract

<i>Objective</i>. 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.<i>Approach</i>. Recent work showed that<i>in-vitro</i>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.<i>Main results</i>. 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.<i>Significance</i>. 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.