The effect of early life status epilepticus on ultrasonic vocalizations in mice

Abstract

Summary Objective Infant crying is a series of innate vocal patterns intended to elicit the attention of adult caregivers for fulfillment of specific needs, such as pain, hunger, or hypostimulation. It is one of the earliest forms of observable communication. In neonatal rodents, this behavior has recently been investigated as a potential early behavioral marker of neural deficits in neurodevelopmental disorders. However, few studies have examined the effects of seizures on vocalization behavior during the neonatal period. The purpose of this study is to investigate the effect of a single kainate-induced early life seizure on vocalization behavior in mice. This study also investigates the subsequent effect of seizures on two pathways critical for early neural development and epileptogenesis: the PI3K-Akt-mTOR and Canonical Wnt intracellular signaling pathways. Methods On postnatal day 10, male and female 129SvEvTac mice received a single intraperitoneal injection of kainic acid (2.5 mg/kg) or vehicle injection. The kainate administration resulted in 1–2 hours of status epilepticus. On postnatal days 11 and 12, the quantity and duration of isolation-induced ultrasonic vocalizations were recorded. Western blotting analyses were performed using male and female pups on postnatal day 12. Results There was significant, male-specific suppression in the quantity and total duration of 50-kHz calls on postnatal day 12 following seizures. The hippocampi of males on this postnatal day also revealed male specific changes in the PI3K-Akt-mTOR intracellular signaling pathway, as well as changes in phosphorylated fragile × mental retardation protein. Significance These findings demonstrate that early life seizures can disrupt communication behavior in neonatal mice.

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

“…Our results are different from previous studies that described a pattern of decreased call duration in both rat and mouse pups [15,16,18]. In the Lopez-Meraz et al, 2014 study, they found a suppression in the number of USVs in PD14 rats.…”

“…In the Lopez-Meraz et al, 2014 study, they found a suppression in the number of USVs in PD14 rats. A similar suppression of USVs was reported in the other two studies, which were conducted in mice [15,16]. One key difference between these studies and the current study is that they used the chemoconvulsant pilocarpine or kainic acid to induce status epilepticus on a single day.…”

“…To assess changes in USV behavior following seizures, we examined USVs on PD12 using the isolation-induced USV paradigm previously described [15,16]. All vocalizations were recorded in the afternoon (between 1 and 5 pm), approximately 24 hours after the last seizure for the HSL paradigm and 48 hours later for the LSL paradigm.…”

“…Previous studies in both mouse and rat models have reinforced the relationship between seizures and communication deficits. A single instance of status epilepticus (SE) can affect qualitative and quantitative aspects of neonatal ultrasonic vocalization (USV) behavior [15][16][17][18]. Our lab has reported male-specific suppression in the quantity and total duration of 50 kHz calls on postnatal day 12 in 129SvEvTac mice following exposure to kainic-acid (KA) induced SE on postnatal day 10 [16].…”

“…A single instance of status epilepticus (SE) can affect qualitative and quantitative aspects of neonatal ultrasonic vocalization (USV) behavior [15][16][17][18]. Our lab has reported male-specific suppression in the quantity and total duration of 50 kHz calls on postnatal day 12 in 129SvEvTac mice following exposure to kainic-acid (KA) induced SE on postnatal day 10 [16]. Using the same KA seizure paradigm and a broader vocalization spectrum recording system, total USV quantity and duration were found to be suppressed on PD12 following SE on PD10 in C57BL/6 mice, as well as changes in calltype production patterns [15].…”