Disrupted in schizophrenia 1 (DISC1) L100P mutants have impaired activity-dependent plasticity in vivo and in vitro
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tp2015206.pdf
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Author(s)
Molinos, I
Petit, E
Bellini, S
O'Tuathaigh, C
Schorova, L
Mitchell, K J
Waddington, J
Gill, M
Corvin, A P
Tropea, Daniela
Date Issued
January 2016
Journal
Translational Psychiatry
Publisher
Nature Publishing Group
Citation
Tropea, D et al. “Disrupted in Schizophrenia 1 (DISC1) L100P Mutants Have Impaired Activity-Dependent Plasticity in Vivo and in Vitro.” Translational Psychiatry 6, 1 (January 2016): e712 © 2017 Macmillan Publishers Limited, part of Springer Nature
Version
Final published version
Abstract
Major neuropsychiatric disorders are genetically complex but share overlapping etiology. Mice mutant for rare, highly penetrant risk variants can be useful in dissecting the molecular mechanisms involved. The gene disrupted in schizophrenia 1 (DISC1) has been associated with increased risk for neuropsychiatric conditions. Mice mutant for Disc1 display morphological, functional and behavioral deficits that are consistent with impairments observed across these disorders. Here we report that Disc1 L100P mutants are less able to reorganize cortical circuitry in response to stimulation in vivo. Molecular analysis reveals that the mutants have a reduced expression of PSD95 and pCREB in visual cortex and fail to adjust expression of such markers in response to altered stimulation. In vitro analysis shows that mutants have impaired functional reorganization of cortical neurons in response to selected forms of neuronal stimulation, but there is no altered basal expression of synaptic markers. These findings suggest that DISC1 has a critical role in the reorganization of cortical plasticity and that this phenotype becomes evident only under challenge, even at early postnatal stages. This result may represent an important etiological mechanism in the emergence of neuropsychiatric disorders.
MIT Department
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Picower Institute for Learning and Memory
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Creative Commons Attribution 4.0 International License
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DOI of Published Version
https://doi.org/10.1038/TP.2015.206
