Related Experiment Video
Updated: Dec 24, 2025
Simultaneous Video-EEG-ECG Monitoring to Identify Neurocardiac Dysfunction in Mouse Models of Epilepsy
Published on: January 29, 2018
Early developmental electroencephalography abnormalities, neonatal seizures, and induced spasms in a mouse model of
Nicholas Rensing1, Kevin J Johnson1, Thomas J Foutz1
1Department of Neurology and Hope Center for Neurological Disorders, Washington University School of Medicine, St Louis, Missouri.
Insights
Neonatal Tsc1GFAP CKO mice exhibit early EEG abnormalities and focal seizures, mirroring tuberous sclerosis complex (TSC) epilepsy development. This model shows promise for studying early epileptogenesis in TSC.
Area of Science:
- Neuroscience
- Genetics
- Epilepsy Research
Background:
- Tuberous sclerosis complex (TSC) is a common genetic disorder causing epilepsy, often presenting in infancy with focal seizures and infantile spasms.
- Existing mouse models lack comprehensive electroencephalographic (EEG) data during early developmental periods relevant to human infantile epilepsy.
- The Tsc1GFAP CKO mouse model is established for TSC epilepsy, but its early developmental seizure characteristics remain undocumented.
Purpose of the Study:
- To investigate early developmental EEG abnormalities and seizure activity, including spasms, in preweanling Tsc1GFAP CKO mice.
- To assess the utility of the Tsc1GFAP CKO mouse model for studying the early stages of epileptogenesis in TSC.
Main Methods:
- Longitudinal video-EEG and electromyographic recordings were conducted on Tsc1GFAP CKO and control mice from postnatal days 9-21.
- Analysis focused on EEG background abnormalities, sleep-wake states, and spontaneous seizures.
- Spasms were induced using varying doses of N-methyl-D-aspartate (NMDA).
Main Results:
- Tsc1GFAP CKO mice displayed excessive EEG discontinuity and slowing, indicating delayed developmental progression compared to controls.
- These mice exhibited increased vigilance state transitions and fragmentation.
- Spontaneous focal seizures were observed in the early neonatal period, and NMDA-induced spasms occurred at a reduced threshold, though spontaneous spasms were not detected.
Conclusions:
- Preweanling Tsc1GFAP CKO mice replicate key early developmental EEG abnormalities, focal seizures, and a heightened propensity for spasms seen in TSC.
- This model is valuable for early mechanistic and therapeutic investigations into epileptogenesis in TSC.
Objective:
Tuberous sclerosis complex (TSC) is one of the most common genetic causes of epilepsy. Seizures in TSC typically first present in infancy or early childhood, including focal seizures and infantile spasms. Infantile spasms in TSC are particularly characteristic in its strong responsiveness to vigabatrin. Although a number of mouse models of epilepsy in TSC have been described, there are very limited electroencephalographic (EEG) or seizure data during the preweanling neonatal and infantile-equivalent mouse periods. Tsc1GFAP CKO mice are a well-characterized mouse model of epilepsy in TSC, but whether these mice have seizures during early development has not been documented. The objective of this study was to determine whether preweanling Tsc1GFAP CKO mice have developmental EEG abnormalities or seizures, including spasms.
Methods:
Longitudinal video-EEG and electromyographic recordings were performed serially on Tsc1GFAP CKO and control mice from postnatal days 9-21 and analyzed for EEG background abnormalities, sleep-wake vigilance states, and spontaneous seizures. Spasms were also induced with varying doses of N-methyl-D-aspartate (NMDA).
Results:
The interictal EEG of Tsc1GFAP CKO mice had excessive discontinuity and slowing, suggesting a delayed developmental progression compared with control mice. Tsc1GFAP CKO mice also had increased vigilance state transitions and fragmentation. Tsc1GFAP CKO mice had spontaneous focal seizures in the early neonatal period and a reduced threshold for NMDA-induced spasms, but no spontaneous spasms were observed.
Significance:
Neonatal Tsc1GFAP CKO mice recapitulate early developmental aspects of EEG abnormalities, focal seizures, and an increased propensity for spasms. This mouse model may be useful for early mechanistic and therapeutic studies of epileptogenesis in TSC.
