The roles of glial phagocytosis in fear memory formation

Abstract

Glial cells and their roles in synapse remodeling have emerged as important actions for brain homeostasis and plasticity. Their roles in the developmental period have been widely studied, however synapse elimination is a continuous process, occurring throughout an individual's lifespan. Given the critical importance of synaptic plasticity in learning and memory, this study explores the impact of glial phagocytosis on memory processes, particularly during memory formation. This thesis posits that glial phagocytosis plays a vital role in memory formation and is essential for the precise regulation of memory dynamics. In this study, I demonstrate that astrocyte phagocytosis of synapses decreases with the induction of fear memory formation. Furthermore, I show that the conditional knockout of astrocytic phagocytosis receptors results in increased inhibitory synapses and reduced cfos+ expression after fear retrieval, accompanied by heightened fear response behaviors. Lastly, I illustrate that mice with a conditional knockout of astrocytic phagocytosis receptors exhibit normal fear extinction behavior, however with significant difference in the scope of change. Thus, this study reveals that the process of fear memory formation influences glial phagocytosis and its subsequent effects on fear behavior and synapse area.