Rationale:
Dravet syndrome (DS) and Developmental and Epileptic Encephalopathies typically cause pharmacoresistant epilepsy and a diverse array of neuropsychiatric disabilities including movement, social, cognitive, and communication difficulties. Speech and communication difficulties are one of the most common concerns reported by caregivers of people with DS. The interaction of neurological changes in DS make communication particularly difficult to study in that cognitive ability, social desire, and fine motor skills are all required to produce language.
DS mouse models exhibit a variety of phenotypes including spontaneous seizures, early mortality, and social deficits, and ataxia in some models. Mice communicate with a variety of distinct call types known as Ultrasonic Vocalizations (USVs). To understand if these models could be useful for studying communication disorders, we quantified USV frequency in juvenile mice of two established models of DS, Scn1a haploinsufficient and Scn1b knockout mice.
Methods:
USVs were measured for 5 minutes in juvenile mice, separated from the dam, in sound-isolation chambers. Scn1b-/- were compared with wild type (WT) Scn1b+/+ littermates; Scn1a+/- mice were compared with WT Scn1a+/+ littermates. Repeated measurements were made at age postnatal day (P)10, prior to the typical onset of epilepsy in both DS models, and P14, after the typical onset of spontaneous seizures.
Results:
At P10, USV frequency and pup weight were equivalent between Scn1b-/- mice and WT. By P14, Scn1b-/- mice had significantly decreased weight (p< 0.0001, two-way ANOVA) compared with WT and showed signs of poor health. At P14, Scn1b-/- mice showed significantly increased USV frequency compared with WT (p< 0.05, Mann-Whitney test).