Decomposing SV2A Function and Dysfunction one Neuron at a Time Article Swipe
Mir-Shahram Safari
,
Matthew C. Weston
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1177/15357597251352976
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1177/15357597251352976
Synaptic Vesicle Glycoprotein 2A Knockout in Parvalbumin and Somatostatin Interneurons Drives Seizures in the Postnatal Mouse Brain Bartholome O, Neirinckx V, De La Brassinne O, Desloovere J, Van Den Ackerveken P, Raedt R, Rogister B. J Neurosci . 2025 Feb 19;45(8):e1169242024. doi: 10.1523/JNEUROSCI.1169-24.2024 . PMID: 39753304; PMCID: PMC11841765. Synaptic vesicle glycoprotein 2A (SV2A) is a presynaptic protein targeted by the anti-seizure drug levetiracetam. One or more of the three SV2 genes is expressed in all neurons and is essential to normal neurotransmission. Loss of SV2A results in a seizure phenotype in mice and mutations in humans are also linked to congenital seizures. How SV2A action impacts the epileptic phenotype remains unclear, especially among the diverse neuronal populations that regulate network excitability. This study explored how brain structure and function are affected by SV2A conditional knockout (SV2A-cKO) in specific neural cell subtypes. We show that SV2A-cKO in all neurons of the postnatal brain triggers lethal seizures, suggesting that the seizures observed in earlier knockout models were not due to aberrant brain development. Similar lethal seizures are detected in mice in which the loss of SV2A is limited to GABAergic neurons, whereas loss in excitatory neurons produces no noticeable phenotype. No apparent gender difference was ever observed. Further investigation revealed that SV2A-cKO in different GABAergic interneuron populations induces seizure, with variable timescales and severity. Most notably SV2A-cKO in parvalbumin interneurons (PV + ) leads to lethal seizures in young animals, while SV2A-cKO in somatostatin (SST) inhibitory neurons results in seizures that were scarcely observed only in adult mice. These results support the crucial role SV2A plays in PV and SST interneurons and suggest that the action of levetiracetam may be due largely to effects on a subset of GABAergic interneurons.
Related Topics
Concepts
Parvalbumin
GABAergic
Neuroscience
Interneuron
Biology
Excitatory postsynaptic potential
Knockout mouse
Conditional gene knockout
Neurotransmission
Inhibitory postsynaptic potential
Neuron
Ganglionic eminence
Phenotype
Internal medicine
Endocrinology
Medicine
Receptor
Genetics
Gene
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1177/15357597251352976
- OA Status
- diamond
- References
- 10
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4412384843
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4412384843Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1177/15357597251352976Digital Object Identifier
- Title
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Decomposing SV2A Function and Dysfunction one Neuron at a TimeWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2025Year of publication
- Publication date
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2025-07-14Full publication date if available
- Authors
-
Mir-Shahram Safari, Matthew C. WestonList of authors in order
- Landing page
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https://doi.org/10.1177/15357597251352976Publisher landing page
- Open access
-
YesWhether a free full text is available
- OA status
-
diamondOpen access status per OpenAlex
- OA URL
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https://doi.org/10.1177/15357597251352976Direct OA link when available
- Concepts
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Parvalbumin, GABAergic, Neuroscience, Interneuron, Biology, Excitatory postsynaptic potential, Knockout mouse, Conditional gene knockout, Neurotransmission, Inhibitory postsynaptic potential, Neuron, Ganglionic eminence, Phenotype, Internal medicine, Endocrinology, Medicine, Receptor, Genetics, GeneTop concepts (fields/topics) attached by OpenAlex
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0Total citation count in OpenAlex
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10Other works algorithmically related by OpenAlex
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| primary_location.raw_source_name | Epilepsy Currents |
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| publication_date | 2025-07-14 |
| publication_year | 2025 |
| referenced_works | https://openalex.org/W2127801604, https://openalex.org/W2003338471, https://openalex.org/W2122573606, https://openalex.org/W4388828765, https://openalex.org/W1978042149, https://openalex.org/W2614237850, https://openalex.org/W3038858613, https://openalex.org/W4406026050, https://openalex.org/W2474320719, https://openalex.org/W2053189341 |
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