Bristow, G. C., Thomson, D. M., Openshaw, R. L. , Mitchell, E. J., Pratt, J. A., Dawson, N. and Morris, B. J. (2020) 16p11 duplication disrupts hippocampal-orbitofrontal-amygdala connectivity, revealing a neural circuit endophenotype for schizophrenia. Cell Reports, 31(3), 107536. (doi: 10.1016/j.celrep.2020.107536) (PMID:32320645)
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Abstract
Chromosome 16p11.2 duplications dramatically increase risk for schizophrenia, but the mechanisms remain largely unknown. Here, we show that mice with an equivalent genetic mutation (16p11.2 duplication mice) exhibit impaired hippocampal-orbitofrontal and hippocampal-amygdala functional connectivity. Expression of schizophrenia-relevant GABAergic cell markers (parvalbumin and calbindin) is selectively decreased in orbitofrontal cortex, while somatostatin expression is decreased in lateral amygdala. When 16p11.2 duplication mice are tested in cognitive tasks dependent on hippocampal-orbitofrontal connectivity, performance is impaired in an 8-arm maze “N-back” working memory task and in a touchscreen continuous performance task. Consistent with hippocampal-amygdala dysconnectivity, deficits in ethologically relevant social behaviors are also observed. Overall, the cellular/molecular, brain network, and behavioral alterations markedly mirror those observed in schizophrenia patients. Moreover, the data suggest that 16p11.2 duplications selectively impact hippocampal-amygdaloid-orbitofrontal circuitry, supporting emerging ideas that dysfunction in this network is a core element of schizophrenia and defining a neural circuit endophenotype for the disease.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Openshaw, Rebecca Louise and Pratt, Dr Judith and Mitchell, Dr Emma and Morris, Professor Brian |
| Authors: | Bristow, G. C., Thomson, D. M., Openshaw, R. L., Mitchell, E. J., Pratt, J. A., Dawson, N., and Morris, B. J. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience |
| Journal Name: | Cell Reports |
| Publisher: | Elsevier (Cell Press) |
| ISSN: | 2211-1247 |
| ISSN (Online): | 2040-2392 |
| Copyright Holders: | Copyright © 2020 The Authors |
| First Published: | First published in Cell Reports 31(3): 107536 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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