Impaired hippocampal-dependent memory and reduced parvalbumin-positive interneurons in a ketamine mouse model of schizophrenia.

Journal Article

The hippocampus of patients with schizophrenia displays aberrant excess neuronal activity which affects cognitive function. Animal models of the illness have recapitulated the overactivity in the hippocampus, with a corresponding regionally localized reduction of inhibitory interneurons, consistent with that observed in patients. To better understand whether cognitive function is similarly affected in these models of hippocampal overactivity, we tested a ketamine mouse model of schizophrenia for cognitive performance in hippocampal- and medial prefrontal cortex (mPFC)-dependent tasks. We found that adult mice exposed to ketamine during adolescence were impaired on a trace fear conditioning protocol that relies on the integrity of the hippocampus. Conversely, the performance of the mice was normal on a delayed response task that is sensitive to mPFC damage. We confirmed that ketamine-exposed mice had reduced parvalbumin-positive interneurons in the hippocampus, specifically in the CA1, but not in the mPFC in keeping with the behavioral findings. These results strengthened the utility of the ketamine model for preclinical investigations of hippocampal overactivity in schizophrenia.

Full Text

Duke Authors

Cited Authors

  • Koh, MT; Shao, Y; Sherwood, A; Smith, DR

Published Date

  • March 2016

Published In

Volume / Issue

  • 171 / 1-3

Start / End Page

  • 187 - 194

PubMed ID

  • 26811256

Electronic International Standard Serial Number (EISSN)

  • 1573-2509

International Standard Serial Number (ISSN)

  • 0920-9964

Digital Object Identifier (DOI)

  • 10.1016/j.schres.2016.01.023

Language

  • eng