Abstract
Impaired cognitive functioning is a core feature of schizophrenia, and is hypothesized to be due to myelination as well as interneuron defects during adolescent prefrontal cortex (PFC) development. Here we report that in the apomorphine-susceptible (APO-SUS) rat model, which has schizophrenia-like features, a myelination defect occurred specifically in parvalbumin interneurons. The adult rats displayed medial PFC (mPFC)-dependent cognitive inflexibility, and a reduced number of mature oligodendrocytes and myelinated parvalbumin inhibitory axons in the mPFC. In the developing mPFC, we observed decreased myelin-related gene expression that persisted into adulthood. Environmental enrichment applied during adolescence restored parvalbumin interneuron hypomyelination as well as cognitive inflexibility. Collectively, these findings highlight that impairment of parvalbumin interneuron myelination is related to schizophrenia-relevant cognitive deficits.
Highlights
Impaired cognitive functioning is a core feature of schizophrenia, and is hypothesized to be due to myelination as well as interneuron defects during adolescent prefrontal cortex (PFC) development
We report that APO-SUS rats display cognitive inflexibility, that interneurons are hypomyelinated during PFC development, and that environmental enrichment during adolescence restores interneuron hypomyelination and rescues cognitive impairment
These findings indicate that medial PFC (mPFC)-linked spatial working memory is impaired in APO-SUS rats
Summary
Impaired cognitive functioning is a core feature of schizophrenia, and is hypothesized to be due to myelination as well as interneuron defects during adolescent prefrontal cortex (PFC) development. Environmental enrichment applied during adolescence restored parvalbumin interneuron hypomyelination as well as cognitive inflexibility These findings highlight that impairment of parvalbumin interneuron myelination is related to schizophrenia-relevant cognitive deficits. Higher cognitive functions, such as working memory and attentional flexibility develop during adolescence, are optimal in early adulthood and are dependent on correct maturation of the prefrontal cortex (PFC)[1]. We report that APO-SUS rats display cognitive inflexibility, that interneurons are hypomyelinated during PFC development, and that environmental enrichment during adolescence restores interneuron hypomyelination and rescues cognitive impairment
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