Disrupted in schizophrenia 1 (DISC1) L100P mutants have impaired activity-dependent plasticity in vivo and in vitro
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 neuro...
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Nature Publishing Group
2017
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| Online Access: | http://hdl.handle.net/1721.1/112610 https://orcid.org/0000-0001-9730-6636 https://orcid.org/0000-0003-2442-5671 |
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| author | Molinos, I Petit, E Bellini, S O'Tuathaigh, C Schorova, L Mitchell, K J Waddington, J Gill, M Corvin, A P Tropea, Daniela Nagakura, Ikue Sur, Mriganka |
| author2 | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences |
| author_facet | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Molinos, I Petit, E Bellini, S O'Tuathaigh, C Schorova, L Mitchell, K J Waddington, J Gill, M Corvin, A P Tropea, Daniela Nagakura, Ikue Sur, Mriganka |
| author_sort | Molinos, I |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T15:14:11Z |
| format | Article |
| id | mit-1721.1/112610 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T15:14:11Z |
| publishDate | 2017 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/1126102022-09-29T13:34:30Z Disrupted in schizophrenia 1 (DISC1) L100P mutants have impaired activity-dependent plasticity in vivo and in vitro Molinos, I Petit, E Bellini, S O'Tuathaigh, C Schorova, L Mitchell, K J Waddington, J Gill, M Corvin, A P Tropea, Daniela Nagakura, Ikue Sur, Mriganka Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Picower Institute for Learning and Memory Tropea, Daniela Nagakura, Ikue Sur, Mriganka 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. 2017-12-05T19:27:17Z 2017-12-05T19:27:17Z 2016-01 2015-10 2017-12-05T18:50:37Z Article http://purl.org/eprint/type/JournalArticle 2158-3188 http://hdl.handle.net/1721.1/112610 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 https://orcid.org/0000-0001-9730-6636 https://orcid.org/0000-0003-2442-5671 http://dx.doi.org/10.1038/TP.2015.206 Translational Psychiatry Creative Commons Attribution 4.0 International License http://creativecommons.org/licenses/by/4.0/ application/pdf Nature Publishing Group Nature |
| spellingShingle | Molinos, I Petit, E Bellini, S O'Tuathaigh, C Schorova, L Mitchell, K J Waddington, J Gill, M Corvin, A P Tropea, Daniela Nagakura, Ikue Sur, Mriganka Disrupted in schizophrenia 1 (DISC1) L100P mutants have impaired activity-dependent plasticity in vivo and in vitro |
| title | Disrupted in schizophrenia 1 (DISC1) L100P mutants have impaired activity-dependent plasticity in vivo and in vitro |
| title_full | Disrupted in schizophrenia 1 (DISC1) L100P mutants have impaired activity-dependent plasticity in vivo and in vitro |
| title_fullStr | Disrupted in schizophrenia 1 (DISC1) L100P mutants have impaired activity-dependent plasticity in vivo and in vitro |
| title_full_unstemmed | Disrupted in schizophrenia 1 (DISC1) L100P mutants have impaired activity-dependent plasticity in vivo and in vitro |
| title_short | Disrupted in schizophrenia 1 (DISC1) L100P mutants have impaired activity-dependent plasticity in vivo and in vitro |
| title_sort | disrupted in schizophrenia 1 disc1 l100p mutants have impaired activity dependent plasticity in vivo and in vitro |
| url | http://hdl.handle.net/1721.1/112610 https://orcid.org/0000-0001-9730-6636 https://orcid.org/0000-0003-2442-5671 |
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