Figure 1.

Aberrant synaptic engulfment by microglia possibly induces synaptic excitatory/inhibitory (E/I) imbalance. (A) In the healthy brain, in which synaptic E/I balance is properly maintained, ramified microglia continuously move their processes, surveying neuronal synapses. (B) In the ventral thalamus of progranulin knockout mice, C1q expression was increased and activated microglia-engulfed inhibitory synapses, causing E/I imbalance (reference [25]). However, it remains unclear why microglia selectively engulfed inhibitory synapses even when both excitatory and inhibitory synapses were tagged by C1q. (C) In the hippocampus of West Nile virus-infected mice, C1q expression was increased and activated microglia possibly engulfed both excitatory and inhibitory presynaptic terminals (reference [26]) because the presynaptic markers used in the study are expressed in both excitatory and inhibitory synapses. Loss of excitatory and inhibitory synapses could result in E/I imbalance (reference [27,28]). However, the mechanism by which neuronal activity tipped toward excitation even when both excitatory and inhibitory presynaptic transmissions were decreased remains unrevealed. The engulfment of presynapses was also increased in the frontal cortex of systemic lupus erythematosus model mice (reference [29]), implying the possible E/I imbalance in this model mice.