Seizure-prone EL/Suz mice exhibit physical and motor delays and heightened locomotor activity in response to novelty during development.

Abstract

Seizure-prone EL/Suz mice have been studied as a model of multifactorial epilepsy for five decades. In prior behavioral studies, EL/Suz mice were shown to exhibit heightened locomotor activity, which implies a state of underlying hyperexcitability. The aim of the present study was to establish the premorbid behavioral development of basic motor skills and activity levels of EL/Suz mice, as compared with DDY mice, the control strain that is not seizure-prone. EL/Suz and DDY pups were monitored from Postnatal Day (PND) 3 to assess body weight, surface righting, negative geotaxis, forelimb grip strength, eye opening, habituation to a novel environment, and exploratory behavior in a two-compartment task. EL/Suz mice weighed less from PNDs 3 to 21 and exhibited delayed surface righting (PNDs 3, 5, 7) and negative geotaxis (PNDs 5, 7, 9) responses. EL/Suz and DDY mice differed in their habituation to a novel environment, with EL/Suz mice exhibiting higher activity, both within a single 10-minute session and across the 3 days of testing. EL/Suz and DDY mice also differed in the two-compartment task, with EL/Suz mice exhibiting increased locomotor activity and spending a greater amount of time in the light compartment. Thus, the present findings reveal that EL/Suz mice exhibit some developmental delays, altered habituation to a novel environment, and increased exploratory activity. Overall, the present results demonstrate that the behavioral and physiological phenotype of seizure-prone EL/Suz mice is deviant more than 2 months before the onset of seizure susceptibility.