Interneuron hypomyelination is associated with cognitive inflexibility in a rat model of schizophrenia

Dorien A. Maas*, Vivian D Eijsink, Marcia Spoelder, Josephus A van Hulten, Peter De Weerd, Judith R. Homberg, Astrid Vallès, Brahim Nait-Oumesmar, Gerard J.M. Martens

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Article number2329
JournalNature Communications
Volume11
Issue number1
DOIs
Publication statusPublished - 11 May 2020

Cite this

Maas, D. A., Eijsink, V. D., Spoelder, M., van Hulten, J. A., De Weerd, P., Homberg, J. R., Vallès, A., Nait-Oumesmar, B., & Martens, G. J. M. (2020). Interneuron hypomyelination is associated with cognitive inflexibility in a rat model of schizophrenia. Nature Communications, 11(1), [2329]. https://doi.org/10.1038/s41467-020-16218-4