A continuous model of physiological prion aggregation suggests a role for Orb2 in gating long-term synaptic information.

Michele Sanguanini,Antonino Cattaneo

doi:10.1098/rsos.180336

Abstract

The regulation of mRNA translation at the level of the synapse is believed to be fundamental in memory and learning at the cellular level. The family of cytoplasmic polyadenylation element binding (CPEB) proteins emerged as an important RNA-binding protein family during development and in adult neurons. Drosophila Orb2 (homologue of mouse CPEB3 protein and of the neural isoform of Aplysia CPEB) has been found to be involved in the translation of plasticity-dependent mRNAs and has been associated with long-term memory. Orb2 protein presents two main isoforms, Orb2A and Orb2B, which form an activity-induced amyloid-like functional aggregate, thought to be the translation-inducing state of the RNA-binding protein. Here we present a first two-states continuous differential model for Orb2A–Orb2B aggregation. This model provides new working hypotheses for studying the role of prion-like CPEB proteins in long-term synaptic plasticity. Moreover, this model can be used as a first step to integrate translation- and protein aggregation-dependent phenomena in synaptic facilitation rules.

Highlights

Different and complex cellular and molecular aspects underlie information learning and memory, even in simple invertebrate models such as Aplysia californica or Drosophila melanogaster [1,2]
We presented a model of continuous differential equations for Orb2-aggregation and mechanisms of synaptic plasticity it may mediate
This synaptic plasticity mechanism has been shown to be important for a paradigm of Long-Term Memory (LTM) in the fly, but the interest of aggregation-dependent synaptic plasticity goes beyond this specific example and could represent a more general mechanism

Summary

Introduction

Different and complex cellular and molecular aspects underlie information learning and memory, even in simple invertebrate models such as Aplysia californica or Drosophila melanogaster [1,2]. A commonly used synaptic rule is derived from STDP for modelling neuronal network simulations [5,6] and increases or decreases the synaptic efficacy according to the time difference in the onset of the preand the post-synaptic activity. This rule usually does not take into account molecular processes which are fundamental in establishing long-term memory, such as the local translation at the synapse [7,8]

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