Table 3.
Microglial genes shown to affect synapses and behavior.
Protein manipulated | KO type | Reported effects | Publications | |
---|---|---|---|---|
Transmembrane proteins | DAP12 | Constitutive | Reduced startle reflex to acoustic stimuli and reduced pre-pulse inhibition; Defective mIPSCs; impaired AMPA receptor accumulation: reduction in TrkB receptors; defective synaptic transmission; defective positioning of Lh6-expressing interneurons in cortical plate of E18.5 | Kaifu et al., 2003; Roumier et al., 2004; Squarzoni et al., 2014 |
CX3CR1 | Constitutive | Defective positioning of Lh6-expressing interneurons in cortical plate of E18.5; increased cell death in cortical layer V; delayed maturation of synapses in barrel cortex; defective synaptic pruning and long-lasting impairments in social behavior and brain connectivity | Ragozzino et al., 2006; Maggi et al., 2011; Paolicelli et al., 2011; Rogers et al., 2011; Ueno et al., 2013; Squarzoni et al., 2014; Zhan et al., 2014 | |
Complement | C1q | Constitutive | Enhanced connectivity and epilepsy | Chu et al., 2010 |
C3 or CR3 | Constitutive | Decreased synaptic engulfment | Schafer et al., 2012 | |
Trophic factors | BDNF | Inducible conditional KO in CX3CR1-expressing cells | Altered synaptic protein levels; impaired spine formation and elimination; lack of training-induced improvement in motor behavior performance | Parkhurst et al., 2013 |
Phagocytosis and autophagy-related proteins | Progranulin | Constitutive | Increased synaptic pruning of C1q-tagged synapses | Lui et al., 2016 |
ATG7 (autophagy related gene 7) | Conditional in lyzsozyme M-expressing cells | Increased dendritic spines; increased synaptic markers; long-lasting effects in sociability and repetitive behaviors | Kim et al., 2016 |
The table summarizes the main genetic factors that have been shown to affect neuronal circuits and behavior via microglia. The reader should consult Section “Genetic Factors Modulating Microglial Activity” for details and discussion.