Maintenance of synaptic plasticity by negative-feedback of synaptic protein elimination: Dynamic modeling of KIBRA- PKM ζ interactions in LTP and memory

bioRxiv [Preprint]. 2024 Sep 27:2024.09.25.614943. doi: 10.1101/2024.09.25.614943.

Abstract

Activity-dependent modifications of synaptic efficacies are a cellular substrate of learning and memory. Current theories propose that the long-term maintenance of synaptic efficacies and memory is accomplished via a positive-feedback loop at the level of production of a protein species or a protein state. Here we propose a qualitatively different theoretical framework based on negative-feedback at the level of protein elimination. This theory is motivated by recent experimental findings regarding the binding of P K M ζ and KIBRA, two synaptic proteins involved in maintenance of memory, and on how this binding affects the proteins' degradation. We demonstrate this theoretical framework with two different models, a simple abstract model to explore generic features of such a process, and an experimentally motivated phenomenological model. The results of these models are qualitatively consistent with existing data, and generate novel predictions that could be experimentally tested to further validate or reject the negative-feedback theory.

Publication types

  • Preprint