Neuronal Activity-Dependent Accumulation of Arc in Astrocytes

Abstract

The immediate-early gene Arc is a master regulator of synaptic plasticity and plays a critical role in memory consolidation. However, there has not been a comprehensive analysis of the itinerary of Arc protein, linking its function at different subcellular locations with corresponding time points after neuronal network activation. When cultured hippocampal neurons are treated with a combination of pharmacological agents to induce long term potentiation, they express high levels of Arc, allowing to study its spatiotemporal distribution. Our experiments show that neuronal activity-induced Arc expression was not restricted to neurons, but that its spatiotemporal dynamics involved a shift to astrocytes at a later timepoint. Specifically, astrocytic Arc is not due to endogenous transcription, but is dependent on the production of neuronal Arc and accumulates potentially via the recently reported intercellular transfer mechanism through Arc capsids. In conclusion, we found that Arc accumulates within astrocytes in a neuronal activity-dependent manner, which is independent of endogenous astrocytic Arc transcription, therefore highlighting the need to study the purpose of this pool of Arc, especially in learning and memory.