Activation of microglia in acute hippocampal slices affects activity-dependent long-term potentiation and synaptic tagging and capture in area CA1.

Activity dependent setting of synaptic tags is critical for the establishment and maintenance of long-term plasticity and its associative properties such as synaptic tagging and capture (STC), a widely studied cellular model of associative memory. Although the known mechanisms of STC such as setting of synaptic tags or distribution of plasticity related proteins (PRPs) are the processes mainly happening within the neuronal compartments, the role of non-neuronal components is still elusive. Here, we report that microglia has a specific role in setting the synaptic tags and thus promotes long-term plasticity and STC. Treatment of hippocampal slices with clodronate, a specific inhibitor of microglia, resulted in an activated morphology of microglia but not of the hippocampal pyramidal neurons, oligodendrocytes or astrocytes. Activation of microglia before or 60 min after the induction of long-term plasticity prevented its maintenance and thus the expression of STC. Interestingly, activation of microglia 2 h after the induction of long-term plasticity neither prevented its maintenance nor its associative interaction with activated nearby synaptic populations. Given the half-life of synaptic tags is until about 60-90 min, activation of microglia beyond this time point while the maintenance phase is still unperturbed, suggests a lack of microglial interference in the synthesis or trigger of plasticity related products. Thus, our study provides the first evidence that microglia play a critical role in the setting of synaptic tags during the early phase of activity dependent plasticity.