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• W4317734041 abstract "Abstract The apicomplexan parasite Toxoplasma gondii has developed mechanisms to establish a central nervous system infection in virtually all warm‐blooded animals. Acute T. gondii infection can cause neuroinflammation, encephalitis, and seizures. Meanwhile, studies in humans, nonhuman primates, and rodents have linked chronic T. gondii infection with altered behavior and increased risk for neuropsychiatric disorders, including schizophrenia. These observations and associations raise questions about how this parasitic infection may alter neural circuits. We previously demonstrated that T. gondii infection triggers the loss of inhibitory perisomatic synapses, a type of synapse whose dysfunction or loss has been linked to neurological and neuropsychiatric disorders. We showed that phagocytic cells (including microglia and infiltrating monocytes) contribute to the loss of these inhibitory synapses. Here, we show that these phagocytic cells specifically ensheath excitatory pyramidal neurons, leading to the preferential loss of perisomatic synapses on these neurons and not those on cortical interneurons. Moreover, we show that infection induces an increased expression of the complement C3 gene, including by populations of these excitatory neurons. Infecting C3‐deficient mice with T. gondii revealed that C3 is required for the loss of perisomatic inhibitory synapses. Interestingly, loss of C1q did not prevent the loss of perisomatic synapses following infection. Together, these findings provide evidence that T. gondii induces changes in excitatory pyramidal neurons that trigger the selective removal of inhibitory perisomatic synapses and provide a role for a nonclassical complement pathway in the remodeling of inhibitory circuits in the infected brain. image" @default.
• W4317734041 created "2023-01-23" @default.
• W4317734041 creator A5000721031 @default.
• W4317734041 creator A5008421334 @default.
• W4317734041 creator A5011830239 @default.
• W4317734041 creator A5012652764 @default.
• W4317734041 creator A5043122243 @default.
• W4317734041 creator A5048676537 @default.
• W4317734041 creator A5084092756 @default.
• W4317734041 date "2023-02-17" @default.
• W4317734041 modified "2023-09-27" @default.
• W4317734041 title "Complement‐dependent loss of inhibitory synapses on pyramidal neurons following <i>Toxoplasma gondii</i> infection" @default.
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