Impaired θ-γ Coupling Indicates Inhibitory Dysfunction and Seizure Risk in a Dravet Syndrome Mouse Model
Impaired θ-γ Coupling Indicates Inhibitory Dysfunction and Seizure Risk in a Dravet Syndrome Mouse Model
Dravet syndrome (DS) is an epileptic encephalopathy that still lacks biomarkers for epileptogenesis and its treatment. Dysfunction of NaV1.1 sodium channels, which are chiefly expressed in inhibitory interneurons, explains the epileptic phenotype. Understanding the network effects of these cellular deficits may help predict epileptogenesis. Here, we studied θ-γ coupling as a potential marker for altered inhibitory functioning and epileptogenesis in a DS mouse model. We found that cortical θ-γ coupling was reduced in both male and female juvenile DS mice and persisted only if spontaneous seizures occurred. θ-γ Coupling was partly restored by cannabidiol (CBD). Locally disrupting NaV1.1 expression in the hippocampus or cortex yielded early attenuation of θ-γ coupling, which in the hippocampus associated with fast ripples, and which was replicated in a computational model when voltage-gated sodium currents were impaired in basket cells (BCs). Our results indicate attenuated θ-γ coupling as a promising early indicator of inhibitory dysfunction and seizure risk in DS.
- Florida Southern College United States
- State University System of Florida United States
- Department of Neurology Netherlands
- University of South Florida United States
- Stichting Epilepsie Instellingen Nederland Netherlands
Cerebral Cortex, Male, Mice, Knockout, Epilepsy, Electroencephalography, Epilepsies, Myoclonic, Hippocampus, NAV1.1 Voltage-Gated Sodium Channel, Mice, Interneurons, Potassium Channels, Voltage-Gated, Seizures, Animals, Cannabidiol, Gamma Rhythm, Anticonvulsants, Computer Simulation, Female, Theta Rhythm, Biomarkers
Cerebral Cortex, Male, Mice, Knockout, Epilepsy, Electroencephalography, Epilepsies, Myoclonic, Hippocampus, NAV1.1 Voltage-Gated Sodium Channel, Mice, Interneurons, Potassium Channels, Voltage-Gated, Seizures, Animals, Cannabidiol, Gamma Rhythm, Anticonvulsants, Computer Simulation, Female, Theta Rhythm, Biomarkers
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