Hippocampal Microglia is critical for Spatial, but not Aversive, Memory establishment

In the healthy adult brain, microglia physically interact with a subset of synapses and contribute to the development, maturation, and remodeling of neural circuits, ultimately influencing behavioral outcomes. We examined how the depletion of hippocampal microglia affects spatial and aversive memories processing. To this end, we administered clodronate into the rat hippocampus, and immunofluorescence analyses were performed to determine the time window and specificity of this microglial-depleting agent. Three days after clodronate infusion, we detected a transient reduction in microglial cell number, while the percentage of area occupied by astrocytes and neurons remained unchanged. At this time point, rats were trained in a spatial object recognition (SOR) task, demonstrating successful acquisition and short-term memory (STM) expression; however, they failed to consolidate the memory. Moreover, microglial depletion before the SOR test did not affect long-term memory (LTM) expression but prevented its reconsolidation. In contrast, when rats were trained in an aversive inhibitory avoidance (IA) task under hippocampal microglial depletion, no impairment was observed in either the acquisition or expression of STM or its subsequent consolidation. Nevertheless, microglial depletion before the IA test did not affect either LTM expression or the extinction process. Thus, our results highlight a differential role for hippocampal microglia in the dynamic processes underlying memory.