Detection of memory engrams in mammalian neuronal circuits

Abstract

It has long been assumed that activity patterns persist in neuronal circuits after they are first experienced, as part of the process of information processing and storage by the brain. However, these “reverberations” of current activity have not been directly observed on a single neuron level in a mammalian system. Here we demonstrate that specific induced activity patterns are retained in mature cultured hippocampal neuronal networks. Neurons within the network are induced to fire at a single frequency or in a more complex pattern containing two distinct frequencies. After the stimulation was stopped, the subsequent neuronal activity of hundreds of neurons in the network was monitored. In the case of single-frequency stimulation, it was observed that many of the neurons continue to fire at the same frequency that they were stimulated to fire at. Using a Recurrent Neural Network (RNN) trained to detect specific, more complex patterns, we found that the multiple-frequency stimulation patterns were also retained within the neuronal network. Moreover, it appears that the component frequencies of the more complex patterns are stored in different populations of neurons and neuron subtypes.

Significance Statement The existence of memory engrams, or reverberations of recently experienced activity patterns, has long been supposed but never directly demonstrated in mammalian neuronal networks. Through the use of highly accessible cultured neuronal networks grown on silicon wafers, stimulated to fire in user-defined patterns using photoconductive stimulation, we have demonstrated their existence and established a paradigm for the analysis of the microcircuitry involved.