Mismatch negativity matures in adolescence and without sensitivity to microglial depletion.

Higher brain functions and cognition undergo extensive development during adolescence, when psychiatric disorders such as schizophrenia typically onset. Understanding how developmental processes during adolescence interact with schizophrenia pathophysiology and risk remains a central goal in psychiatry. Here we focus on mismatch negativity, a well-established biomarker of schizophrenia, and show that a key component of mismatch negativity, "deviance detection", emerges during adolescence in mouse primary visual cortex, along with a refinement of fronto-visual functional connectivity. In contrast, we found stimulus-specific adaptation-another component of mismatch negativity-to be present prior to adolescence. Because microglia are implicated in schizophrenia risk and disease states, we further investigated what role microglia may play in the development of mismatch responses under physiological conditions. We found that microglial depletion with PLX5622 in adolescence arrests the development of resting oscillations in frontal areas, but does not affect the development of deviance detection, other signatures of visual context processing, or prefrontal-visual functional connectivity. Our findings suggest (a) a key component of mismatch negativity develops in adolescence, a period of vulnerability to schizophrenia, and (b) the development underlying this component does not require robust microglia activity, clarifying the developmental role of microglia in higher-order visual processing.