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Cortical circuit dysfunction in a mouse model of alpha-synucleinopathy in vivo
Considerable fluctuations in cognitive performance and eventual dementia are an important characteristic of alpha-synucleinopathies, such as Parkinson’s disease and Lewy Body dementia and are linked to cortical dysfunction. The presence of misfolded and aggregated alpha-synuclein in the cerebral cor...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8643497/ https://www.ncbi.nlm.nih.gov/pubmed/34877534 http://dx.doi.org/10.1093/braincomms/fcab273 |
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author | Blumenstock, Sonja Sun, Fanfan Klaus, Carolin Marinković, Petar Sgobio, Carmelo Paeger, Lars Liebscher, Sabine Herms, Jochen |
author_facet | Blumenstock, Sonja Sun, Fanfan Klaus, Carolin Marinković, Petar Sgobio, Carmelo Paeger, Lars Liebscher, Sabine Herms, Jochen |
author_sort | Blumenstock, Sonja |
collection | PubMed |
description | Considerable fluctuations in cognitive performance and eventual dementia are an important characteristic of alpha-synucleinopathies, such as Parkinson’s disease and Lewy Body dementia and are linked to cortical dysfunction. The presence of misfolded and aggregated alpha-synuclein in the cerebral cortex of patients has been suggested to play a crucial role in this process. However, the consequences of a-synuclein accumulation on the function of cortical networks at cellular resolution in vivo are largely unknown. Here, we induced robust a-synuclein pathology in the cerebral cortex using the striatal seeding model in wild-type mice. Nine months after a single intrastriatal injection of a-synuclein preformed fibrils, we observed profound alterations of the function of layer 2/3 cortical neurons in somatosensory cortex by in vivo two-photon calcium imaging in awake mice. We detected increased spontaneous activity levels, an enhanced response to whisking and increased synchrony. Stereological analyses revealed a reduction in glutamic acid decarboxylase 67-positive inhibitory neurons in the somatosensory cortex of mice injected with preformed fibrils. Importantly, these findings point to a disturbed excitation/inhibition balance as a relevant driver of circuit dysfunction, potentially underlying cognitive changes in alpha-synucleinopathies. |
format | Online Article Text |
id | pubmed-8643497 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-86434972021-12-06 Cortical circuit dysfunction in a mouse model of alpha-synucleinopathy in vivo Blumenstock, Sonja Sun, Fanfan Klaus, Carolin Marinković, Petar Sgobio, Carmelo Paeger, Lars Liebscher, Sabine Herms, Jochen Brain Commun Original Article Considerable fluctuations in cognitive performance and eventual dementia are an important characteristic of alpha-synucleinopathies, such as Parkinson’s disease and Lewy Body dementia and are linked to cortical dysfunction. The presence of misfolded and aggregated alpha-synuclein in the cerebral cortex of patients has been suggested to play a crucial role in this process. However, the consequences of a-synuclein accumulation on the function of cortical networks at cellular resolution in vivo are largely unknown. Here, we induced robust a-synuclein pathology in the cerebral cortex using the striatal seeding model in wild-type mice. Nine months after a single intrastriatal injection of a-synuclein preformed fibrils, we observed profound alterations of the function of layer 2/3 cortical neurons in somatosensory cortex by in vivo two-photon calcium imaging in awake mice. We detected increased spontaneous activity levels, an enhanced response to whisking and increased synchrony. Stereological analyses revealed a reduction in glutamic acid decarboxylase 67-positive inhibitory neurons in the somatosensory cortex of mice injected with preformed fibrils. Importantly, these findings point to a disturbed excitation/inhibition balance as a relevant driver of circuit dysfunction, potentially underlying cognitive changes in alpha-synucleinopathies. Oxford University Press 2021-11-15 /pmc/articles/PMC8643497/ /pubmed/34877534 http://dx.doi.org/10.1093/braincomms/fcab273 Text en © The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Blumenstock, Sonja Sun, Fanfan Klaus, Carolin Marinković, Petar Sgobio, Carmelo Paeger, Lars Liebscher, Sabine Herms, Jochen Cortical circuit dysfunction in a mouse model of alpha-synucleinopathy in vivo |
title | Cortical circuit dysfunction in a mouse model of alpha-synucleinopathy in vivo |
title_full | Cortical circuit dysfunction in a mouse model of alpha-synucleinopathy in vivo |
title_fullStr | Cortical circuit dysfunction in a mouse model of alpha-synucleinopathy in vivo |
title_full_unstemmed | Cortical circuit dysfunction in a mouse model of alpha-synucleinopathy in vivo |
title_short | Cortical circuit dysfunction in a mouse model of alpha-synucleinopathy in vivo |
title_sort | cortical circuit dysfunction in a mouse model of alpha-synucleinopathy in vivo |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8643497/ https://www.ncbi.nlm.nih.gov/pubmed/34877534 http://dx.doi.org/10.1093/braincomms/fcab273 |
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