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bioRxiv · 10.1101/2021.12.23.473965

Crosstalk between biochemical signaling and trafficking determines AMPAR dynamics in synaptic plasticity

Bell, M.·Rangamani, P.
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Abstract

Synaptic plasticity involves the modification of both biochemical and structural components of neurons. Many studies have revealed that the change in the number density of the glutamatergic receptor AMPAR at the synapse is proportional to synaptic weight update; increase in AMPAR corresponds to strengthening of synapses while decrease in AMPAR density weakens synaptic connections. The dynamics of AMPAR are thought to be regulated by upstream signaling, primarily the calcium-CaMKII pathway, trafficking to and from the synapse, and influx from extrasynaptic sources. Here, we have developed a set of models using compartmental ordinary differential equations to systematically investigate contributions of signaling and trafficking variations on AMPAR dynamics at the synaptic site. We find that the model properties including network architecture and parameters significantly affect the integration of fast upstream species by slower downstream species. Furthermore, we predict that the model outcome, as determined by bound AMPAR at the synaptic site, depends on (a) the choice of signaling model (bistable CaMKII or monostable CaMKII dynamics), (b) trafficking versus influx contributions, and (c) frequency of stimulus. Therefore, AMPAR dynamics can have unexpected dependencies when upstream signaling dynamics (such as CaMKII and PP1) are coupled with trafficking modalities.

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Bell, M., Rangamani, P.. 2021-12-23. Crosstalk between biochemical signaling and trafficking determines AMPAR dynamics in synaptic plasticity. https://doi.org/10.1101/2021.12.23.473965

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