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Multiple Early-Life Seizures Alters Neonatal Communicative Behavior in Fmr1 Knockout Mice
Phuoc H Nguyen1, David A Narvaiz1, Paige D Womble1
1Department of Psychology and Neuroscience, Baylor University, Waco, Texas, USA.
Insights
Early-life seizures impair communication in Fragile X syndrome (FXS) mouse models. Seizures altered ultrasonic vocalizations, with FXS mice showing additional deficits, highlighting communication impairments in this condition.
Area of Science:
- Neuroscience
- Developmental Biology
- Genetics
Background:
- Fragile X syndrome (FXS) is a leading genetic cause of intellectual disability and autism spectrum disorder.
- Seizures are a common comorbidity in individuals with FXS, impacting development.
- Neonatal communicative behavior is crucial for social development and can be affected by early-life events.
Purpose of the Study:
- To investigate the impact of early-life seizures on neonatal communicative behavior in a mouse model of Fragile X syndrome (FXS).
- To determine if seizures exacerbate communication deficits in Fmr1 knockout mice.
Main Methods:
- Administered daily flurothyl seizures to Fmr1 knockout and wild-type mice from postnatal day 7 to 11.
- Recorded and analyzed ultrasonic vocalizations on postnatal day 12.
- Compared spectral and temporal acoustic features between seizure and control groups.
Main Results:
- Seizures significantly altered ultrasonic vocalizations in both genotypes, increasing call duration, fundamental frequency, and cumulative call duration.
- Seizure induction decreased vocalization latency and mean power, while increasing specific call types (downward, frequency-step).
- Fmr1 knockout mice with seizures exhibited a unique increase in chevron calls, indicating genotype-specific vocal deficits.
Conclusions:
- Early-life seizures induce significant communication impairments in neonatal mice.
- Seizures superimposed on the Fmr1 knockout genotype lead to additional, distinct vocalization deficits.
- These findings underscore the critical impact of seizures on communication development in FXS.
Abstract:
Fragile X syndrome (FXS) is the leading monogenic cause of intellectual disability and a significant contributor to Autism Spectrum Disorder. Individuals with FXS are subject to developing numerous comorbidities, one of the most prevalent being seizures. In the present study, we investigated how seizures affected neonatal communicative behavior in the FXS mouse model. On postnatal day (PD) 7 through 11, we administered 3 flurothyl seizures per day to both Fmr1 knockout and wild-type C57BL/6J male mice. Ultrasonic vocalizations were recorded on PD12. Statistically significant alterations were found in both spectral and temporal measurements across seizure groups. We found that induction of seizures across PD7-11 resulted in an increased fundamental frequency (pitch) of ultrasonic vocalizations produced (p < 0.05), a longer duration of calls (p < 0.05), and a greater cumulative duration of calls (p < 0.05) in both genotypes. Induction of seizures across PD7-11 also resulted in a decreased latency to the first emitted vocalization (p < 0.05) and a decrease in mean power (loudness) for their vocalizations (p < 0.05). Early-life seizures also resulted in an increase in the number of downward and frequency step call types (p < 0.05). There was a significant increase in the number of chevron calls emitted from the Fmr1 knockout mice that received seizures compared to knockout control and wild-type seizure mice (p < 0.05). Overall, this study provides evidence that early-life seizures result in communication impairments and that superimposing seizures in Fmr1 knockout mice does produce an additional deficit in vocalization.
