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.


“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.

  • What is the minimum anatomical substrate of a reverberatory circuit
    capable of persistent neural activity?
  • Is persistent activity primarily sustained by synaptic reverberation, or by
    bistable dynamics of single neurons?
  • What is the NMDA:AMPA ratio at recurrent synapses of association
    cortices, especially in the prefrontal cortex?
  • How does this ratio depend on the frequency of repetitive stimulation
    and on neuromodulation?
  • What are the negative feedback mechanisms responsible for the rate
    control in a working memory network?
  • Is delay period activity asynchronous between neurons, or does it display
    partial network synchrony and coherent oscillations?
  • Is delay period activity more sensitive to NMDAR antagonists compared
    with AMPAR antagonists?
  • Does persistent activity disappear in an abrupt fashion, with a graded
    block of NMDAR and AMPAR channels, as predicted by the attractor
  • How significant are drifts of persistent activity during working memory?
    Are drifts random or systematic over trials?
  • What are the biological mechanisms underlying the robustness of a
    memory network with a continuum of persistent activity patterns?
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