Mismatch negativity matures in adolescence and without sensitivity to microglial depletion

12/09/2026

AI Summary

Deviance detection component of mismatch negativity emerges during adolescence in mouse primary visual cortex, alongside refinement of fronto-visual functional connectivity.
Stimulus-specific adaptation is present before adolescence, indicating distinct developmental timelines for mismatch negativity components.
Microglial depletion during adolescence halts development of frontal resting oscillations but does not impair deviance detection or prefrontal-visual connectivity.

AI Summary

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.

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.

Basic summary

Neuropsychopharmacology. 2026 Sep 12. doi: 10.1038/s41386-026-02547-3. Online ahead of print.

ABSTRACT

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.

PMID:42728333 | DOI:10.1038/s41386-026-02547-3

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