Abstracts

Rationale: The Kcna-1 null mutant mouse, which lacks the voltage-gated potassium channel subunit Kv1.1, exhibits spontaneous seizures. Seizures typically start around P30 and progress, sometimes resulting in death from status epilepticus. We here describe seizure phenotypes that are unique in this model, their unique progression and sleep-wake patterns of seizures that are dependent on lighting conditions.Methods: After obtaining approval from the Institutional Animal Care and Use Committee, kcna-1 knock out mice (n=12) were surgically implanted with frontal and parietal epidural EEG recording electrodes as well as a nuchal EMG electrode that were secured with dental acrylic around P30. The animals were allowed to recover for at least 3 days and were then hooked up to video EEG recording (XL-Tech, USA) to record seizures and sleep-wake patterns while they are housed in Plexiglas cages. Mice were housed in one of 3 different lighting conditions; 5 days of LD (12 hrs light and 12 hrs dark) followed by 5 days of DD (constant darkness) (n=5); 5 days of DD followed by 5 days of LD (n=5) or 10 days of LD (n=3), with 1 day interval (6th day) to allow acclimation during transitions. Acquired raw video EEG data was visually analyzed for seizures and was transformed to EDF format and uploaded to an automated sleep scoring software (Sirenia sleep- Pinnacle technologies, Inc) to score sleep and wake patterns.Results: A total of 569 seizures were recorded with a mean of 47±18 seizures over the 10 days. Four different seizure phenotypes were seen; Type 1 consisting of behavioral pause followed by wandering and hind limb stretching; Type 2 begin as type 1 but would end in wild running; Type3 consisting of behavioral arrest followed by forelimb clonus and type 4 consisting of generalized tonic-clonic seizures. In total there were 395 Type 1, 49 Type 2, 50 of Type 3 and 75 Type 4 seizures across the 10 days of recording. Regardless of lighting conditions the majority of the Type 4 seizures occurred in the first 5 days and there was also a progressive increase in frequency of seizures with the most prominent seizure phenotype in second 5 days being Type 1. On analysis of sleep wake patterns, majority of seizures occurred while awake (113 vs 80) when housed in LD followed by DD, but majority of seizures occurred in NREM sleep (116 vs 41) when housed in DD followed by LD. Finally when animals were in 10 days of LD, seizures were equally distributed in sleep and wake (86 vs 83). It is noteworthy that many seizures occurred at the transition of wake to sleep, such a seizure would occur within 20 seconds of falling asleep.Conclusions: In conclusion Kcna-1 null mutant mice have unique seizure phenotypes and a unique natural progression of seizures with GTC seizures being most prominent at onset and milder type 4 seizures being most prominent later. Additionally seizures have interesting sleep-wake pattern which is somewhat dependent on the lighting condition.