High seizure load during sensitive periods of development leads to broad shifts in ultrasonic vocalization behavior in neonatal male and female C57BL/6J mice

Abstract

There is increasing evidence that seizures during early development can impact ultrasonic vocalizations (USVs) emitted from neonatal mice. However, most of the effects of early-life seizures have been reported using chemoconvulsants that produce continuous seizures (status epilepticus). In the present study, we evaluated the impact of different seizure frequency loads during early-life vocalization development in C57BL/6J male and female mice. For the high seizure load (HSL) paradigm, we administered 3 flurothyl seizures to mice on postnatal day (PD) 7 through PD11, and recorded USVs on PD12. We found that the induction of seizures across PD7–11 resulted in increased average duration (P < 0.05) and cumulative duration (P < 0.05) of USVs across both sexes. Call-type analyses indicated several call-type changes, including reduced production of complex call-types from males' HSL condition. For the low seizure load (LSL) paradigm, we induced 3 flurothyl seizures only on PD10 and recorded USVs on PD12. We found no change in any spectral or temporal features of USVs. However, call-type production analyses indicated that both male and female animals from the LSL paradigm also produced changes in call-types. This study provides evidence that the magnitude of communication impairment following seizures is significantly impacted by seizure frequency load early in development.