Journal article
Interneuron Desynchronization Precedes Seizures in a Mouse Model of Dravet Syndrome
JOURNAL OF NEUROSCIENCE, v 40(13), pp 2764-2775
25 Mar 2020
PMID: 32102923
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Recurrent seizures, which define epilepsy, are transient abnormalities in the electrical activity of the brain. The mechanistic basis of seizure initiation, and the contribution of defined neuronal subtypes to seizure pathophysiology, remains poorly understood. We performed in vivo two-photon calcium imaging in neocortex during temperature-induced seizures in male and female Dravet syndrome (Scn1a(+/-)) mice, a neurodevelopmental disorder with prominent temperature-sensitive epilepsy. Mean activity of both putative principal cells and parvalbumin-positive interneurons (PV-INs) was higher in Scn1a(+/-) relative to wild-type controls during quiet wakefulness at baseline and at elevated core body temperature. However, wild-type PV-INs showed a progressive synchronization in response to temperature elevation that was absent in PV-INs from Scn1a(+/-) mice. Hence, PV-IN activity remains intact interictally in Scn1a(+/-) mice, yet exhibits decreased synchrony immediately before seizure onset. Wesuggest that impaired PV-IN synchronization may contribute to the transition to the ictal state during temperature-induced seizures in Dravet syndrome.
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Details
- Title
- Interneuron Desynchronization Precedes Seizures in a Mouse Model of Dravet Syndrome
- Publication Details
- JOURNAL OF NEUROSCIENCE, v 40(13), pp 2764-2775
- Publisher
- SOC NEUROSCIENCE; WASHINGTON
- Number of pages
- 0
- Grant note
- This work was supported by an American Academy of Neurology Medical Student Summer Research Scholarship to C.H.T.; National ScienceFoundation (NSF) NCS-FOAwardSMA-1734795 to S.F.M.; and NIH NINDS research Grants K08 NS097633 and R01 NS110869, NSF NCS-FO Award SMA-1734813, and the Dana Foundation David Mahoney Neuroimaging Program and the Burroughs Wellcome Fund Career Award for Medical Scientists to E.M.G. We thank Dr. Eric D. Marsh for assistance with electrocorticography, Joanna H. Mattis for comments on a prior version of this paper, Dr. Jennifer A. Kearney at Northwestern University for the generous gift of Scn1a+/- mice, and Loren Looger, GENIE Project, Janelia Research Campus of the HHMI, for distribution of GCaMP6.
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Drexel University
- Web of Science ID
- WOS:000521825000015
- Scopus ID
- 2-s2.0-85082542751
- Other Identifier
- 991021860774704721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Neurosciences