Neuronal hyperactivity in neurons derived from individuals with gray matter heterotopia Article Swipe
Francesco Di Matteo
,
Rebecca Bonrath
,
Veronica M. Pravatà
,
Hanna Schmidt
,
Ane Cristina Ayo Martin
,
Rossella Di Giaimo
,
Danusa Menegaz
,
Stephan Riesenberg
,
Femke M.S. de Vrij
,
Giuseppina Maccarrone
,
Maria Holzapfel
,
Tobias Straub
,
Steven A. Kushner
,
Stephen P. Robertson
,
Matthias Eder
,
Silvia Cappello
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1038/s41467-025-56998-1
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1038/s41467-025-56998-1
Periventricular heterotopia (PH), a common form of gray matter heterotopia associated with developmental delay and drug-resistant seizures, poses a challenge in understanding its neurophysiological basis. Human cerebral organoids (hCOs) derived from patients with causative mutations in FAT4 or DCHS1 mimic PH features. However, neuronal activity in these 3D models has not yet been investigated. Here we show that silicon probe recordings reveal exaggerated spontaneous spike activity in FAT4 and DCHS1 hCOs, suggesting functional changes in neuronal networks. Transcriptome and proteome analyses identify changes in neuronal morphology and synaptic function. Furthermore, patch-clamp recordings reveal a decreased spike threshold specifically in DCHS1 neurons, likely due to increased somatic voltage-gated sodium channels. Additional analyses reveal increased morphological complexity of PH neurons and synaptic alterations contributing to hyperactivity, with rescue observed in DCHS1 neurons by wild-type DCHS1 expression. Overall, we provide new comprehensive insights into the cellular changes underlying symptoms of gray matter heterotopia.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1038/s41467-025-56998-1
- OA Status
- gold
- Cited By
- 2
- References
- 55
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4407691742
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4407691742Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1038/s41467-025-56998-1Digital Object Identifier
- Title
-
Neuronal hyperactivity in neurons derived from individuals with gray matter heterotopiaWork title
- Type
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articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2025Year of publication
- Publication date
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2025-02-18Full publication date if available
- Authors
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Francesco Di Matteo, Rebecca Bonrath, Veronica M. Pravatà, Hanna Schmidt, Ane Cristina Ayo Martin, Rossella Di Giaimo, Danusa Menegaz, Stephan Riesenberg, Femke M.S. de Vrij, Giuseppina Maccarrone, Maria Holzapfel, Tobias Straub, Steven A. Kushner, Stephen P. Robertson, Matthias Eder, Silvia CappelloList of authors in order
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https://doi.org/10.1038/s41467-025-56998-1Publisher landing page
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YesWhether a free full text is available
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goldOpen access status per OpenAlex
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-
https://doi.org/10.1038/s41467-025-56998-1Direct OA link when available
- Concepts
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Neuroscience, Transcriptome, Premovement neuronal activity, Biology, Electrophysiology, Patch clamp, Gene expression, Genetics, GeneTop concepts (fields/topics) attached by OpenAlex
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-
2Total citation count in OpenAlex
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2025: 2Per-year citation counts (last 5 years)
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10Other works algorithmically related by OpenAlex
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