Early-life status epilepticus acutely impacts select quantitative and qualitative features of neonatal vocalization behavior: Spectrographic and temporal characterizations in C57BL/6 mice

Abstract

Early-life seizures are known to cause long-term deficits in social behavior, learning, and memory, however little is known regarding their acute impact. Ultrasonic vocalization (USV) recordings have been developed as a tool for investigating early communicative deficits in mice. Previous investigation from our lab found that postnatal day (PD) 10 seizures cause male-specific suppression of 50-kHz USVs on PD12 in 129 SvEvTac mouse pups. The present study extends these findings by spectrographic characterization of USVs following neonatal seizures. On PD10, male C57BL/6 pups were administered intraperitoneal injections of kainic acid or physiological saline. On PD12, isolation-induced recordings were captured using a broad-spectrum ultrasonic microphone. Status epilepticus significantly suppressed USV quantity (p=0.001) and total duration (p<0.05). Seizure pups also utilized fewer complex calls than controls (p<0.05). There were no changes in call latency or inter-call intervals. Spectrographic analysis revealed increased peak amplitude for complex, downward, short, two-syllable, and upward calls, as well as reduced mean duration for short and two-syllable calls in seizure mice. This investigation provides the first known spectrographic characterization of USVs following early-life seizures. These findings also enhance evidence for USVs as an indicator of select communicative impairment.

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.…”

“…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.…”

“…Sampling frequency was set at 22050. Additionally, call-types were manually identified by an experimenter blinded to treatment identity, using previously described classification scheme [15]. For HSL paradigm, all animals vocalized during the recording period and none were excluded from analysis (n male control = 7, n female control = 12, n male seizure = 8, n female seizure = 10).…”

“…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]. These findings suggest that a single episode of SE on PD10 is sufficient to produce changes in communication behavior during development.…”

“…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].…”