Synaptic reverberation underlying mnemonic persistent activity

This is a review article published in TRENDS in Neurosciences by Xiao-Jing Wang in 2001.

The following two sentences from the abstract summarize the entire review nicely.

Stimulus-specific persistent neural activity is the neural process underlying active (working) memory. Since its discovery 30 years ago, mnemonic activity has been hypothesized to be sustained by synaptic reverberation in a recurrent circuit.

Introduction

“The obligatory physical process underlying active (working) memory is persistent neural activity that is sustained internally in the brain, rather than driven by inputs from the external world.”

I suppose I understand the message being portrayed here, but this sentence hints that there is some internal process that is “choosing” to drive the recurrent activity. The way I see it, external activity is driving, or initially drove, the internal process that is sustaining the recurrent activity. However indirectly, I believe it is external stimuli which drives the recurrent activity, otherwise we would have a rather catastrophic existential crisis on our hands!

How localized can it be?

Back in 2001 the idea was that these reciprocal networks were formed across many brain regions not in local regions. Or in other words, we might “see” or record consistent activity from a small region in the neocortex, but the recurrent activity is not contained in that small region. While the majority of activity is there, perhaps representing the memory, there are signals being sent across many brain regions. An interesting study would be to cut off connection between some of these hypothesized regions and explore the effect on the patient’s working memory. That being said here is an excerpt from the paper just after having explained the above

“Experiments and biophysical modeling on the neural basis of persistent activity have so far been focused on the scenario of reverberation within a brain area. The present article will be confined to synaptic mechanisms in a local recurrent network.”

Attractor paradigms

This part was nice. Since the 1970′s they’ve been considering ‘dynamical attractors’ as plausible explanations for the delay activity patterns observed. As of 2001 he said

It is only recently, beginning with the work by Amit and colleagues, that attractor network models have been implemented with realistic models of cortical neurons and synapses

This is great because I found more papers where actualy models and simulations were performed. Note to self: Check out Amit DJ‘s work.

NMDA receptors and the stability of a memory network

Apparently, the recurrent activity necessary to give rise to working memory behavior is “easier to realize” if the network’s synapses are primarily voltage-gated NMDA receptors. This is due to many things, such as the fact that AMPAR-mediated EPSCs are about three times faster than the GABA receptor-mediated IPSCs.

I was very happy to see a box containing outstanding questions at the end of the paper. I will paste them here for posterity.

Recent theoretical models have raised several neurophysiological questions that can be investigated experimentally. Answers to these questions will help to elucidate the mechanisms of neural persistent activity.