Review for "Competition for a limited supply of synaptic building blocks predicts multiplicative synaptic normalization and heterosynaptic plasticity"

Completed on 21 Aug 2017 by Friedemann Zenke. Sourced from

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Having thought about putative rapid compensatory processes for quite some time now, I greatly appreciate modeling efforts in this direction and I read this preprint with great interest. The model’s simplicity is appealing and its behavior intuitively makes sense. I thought of sharing some of my thoughts that I jotted down while skimming through the manuscript.

First, I was wondering about the notion and importance of a single shared receptor pool in the model. If I understand the model correctly, a strong LTP event at one synapse creates some kind of “vacuum” which then causes depression at other synapses by depleting the shared pool. However, from what I recall from most mechanistic models for the induction of early phase LTP, the assumption generally seem to be that the receptors which are inserted into the postsynaptic density are already present at the synapse or its immediate vicinity. This seems to slightly deviate from the notion of a single shared pool. However, on the slower timescales of receptor trafficking, a shared pool seems a pretty reasonable assumption. I guess this could in principle be modeled as a combination of localized synapse specific pools that are coupled on a slower timescale. However, such a slower coupling may introduce additional lag and have other side unwanted side effects. I was wondering whether the authors have thought about this and if they think it would affect their main findings in any way.
Second, there is at least some experimental evidence (Oh et al., 2015) suggesting that synaptic competition for a shared resource is *not* the cause of synaptic normalization, but that rather third messengers are involved. I was wondering what the authors think about this and whether the model could be “re-interpreted” or “re-invented” for such a third messenger scenario.
Third, while reading I was reminded of the study by Delattre et al. (2015) which has pitched a similar idea of competition for a shared resource. This might or might not be relevant to the study. If I remember correctly, the study was based on a direct comparison to experimental data.

* Oh, W.C., Parajuli, L.K., and Zito, K. (2015). Heterosynaptic Structural Plasticity on Local Dendritic Segments of Hippocampal CA1 Neurons. Cell Reports 10, 162–169.
* Delattre, V., Keller, D., Perich, M., Markram, H., and Muller, E.B. (2015). Network-timing-dependent plasticity. Front. Cell. Neurosci. 220.