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. 2022 Aug 8;15:965756. doi: 10.3389/fnmol.2022.965756

FIGURE 2.

FIGURE 2

Genetic, environmental and microglial influences on synaptic connectivity in development and disease. (A,B) Immune and neuronal factors (Gauthier et al., 2010; Marín, 2012; Nieto et al., 2013; Volk and Lewis, 2013b; El-Ansary and Al-Ayadhi, 2014; McAllister, 2014; English et al., 2015; Estes and McAllister, 2015; Sinclair et al., 2016; Ishizuka et al., 2017; Gao et al., 2018; Jiang et al., 2018; Huang et al., 2019; Trossbach et al., 2019; Wiebe et al., 2019; Barbosa et al., 2020; Chen et al., 2020; Boukouaci et al., 2021) known to be altered in ASD and SZ. Purple text represents elements that are affected in both disorders. (C) Open question: to what extent do bidirectional microglia-neuron interactions regulate synaptic connectivity? (D,E). Microglia regulate excitatory and inhibitory connectivity during healthy development. (F) In the context of genetic and environmental risk factors, microglia alter their phenotypes and contribute to altered synaptic connectivity. Many open questions remain, especially regarding the role of microglia in mediating maladaptive changes in inhibitory synaptic connectivity.