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Cell. 2019 Sep 5;178(6):1387-1402.e14. doi: 10.1016/j.cell.2019.07.023. Epub 2019 Aug 29.

Long-Lasting Rescue of Network and Cognitive Dysfunction in a Genetic Schizophrenia Model.

Author information

1
Friedrich Miescher Institute, 4058 Basel, Switzerland.
2
Departments of Psychiatry and Genetic Medicine, School of Medicine, University of Geneva, 1201 Geneva, Switzerland.
3
Friedrich Miescher Institute, 4058 Basel, Switzerland. Electronic address: caroni@fmi.ch.

Abstract

Although sensitizing processes occur earlier, schizophrenia is diagnosed in young adulthood, which suggests that it might involve a pathological transition during late brain development in predisposed individuals. Parvalbumin (PV) interneuron alterations have been noticed, but their role in the disease is unclear. Here we demonstrate that adult LgDel+/- mice, a genetic model of schizophrenia, exhibit PV neuron hypo-recruitment and associated chronic PV neuron plasticity together with network and cognitive deficits. All these deficits can be permanently rescued by chemogenetic activation of PV neurons or D2R antagonist treatments, specifically in the ventral hippocampus (vH) or medial-prefrontal cortex during a late-adolescence-sensitive time window. PV neuron alterations were initially restricted to the hippocampal CA1/subiculum, where they became responsive to treatment in late adolescence. Therefore, progression to disease in schizophrenia-model mice can be prevented by treatments supporting vH-mPFC PV network function during a sensitive time window late in adolescence, suggesting therapeutic strategies to prevent the outbreak of schizophrenia.

PMID:
31474363
DOI:
10.1016/j.cell.2019.07.023

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