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Updated: Aug 12, 2025
A Behavioral Screen for Heat-Induced Seizures in Mouse Models of Epilepsy
Published on: July 12, 2021
Augmented impulsive behavior in febrile seizure-induced mice
Chilly Gay Remonde1, Edson Luck Gonzales1, Keremkleroo Jym Adil1
1School of Medicine and Center for Neuroscience Research, Konkuk University, Seoul, 05029 Republic of Korea.
Insights
Febrile seizures (FS) in mice, particularly recurrent ones, can lead to increased impulsivity and anxiety-like behavior, especially in males. These changes are linked to alterations in serotonin system genes, suggesting potential long-term neurodevelopmental effects.
Area of Science:
- Neuroscience
- Developmental Biology
- Behavioral Science
Background:
- Febrile seizures (FS) are common in childhood, affecting 2-5% of young children.
- The long-term neurodevelopmental consequences of FS are not fully understood, with limited laboratory evidence.
- Comparative studies using both male and female animal models for FS effects are scarce.
Purpose of the Study:
- To investigate the impact of induced febrile seizures (FS) on the behavioral characteristics of male and female mice.
- To compare the effects of single versus recurrent FS on subsequent behavior.
- To explore potential underlying genetic mechanisms related to impulsivity.
Main Methods:
- Hyperthermic seizures were induced in male and female ICR mice using an infrared heat lamp at specific postnatal days.
- Mice received either a single FS or three FS over a short period.
- Behavioral tests, including elevated plus maze and cliff avoidance, were conducted starting at postnatal day 30.
- Gene expression analysis of impulsivity-related genes was performed on prefrontal cortex tissue.
Main Results:
- FS-induced mice did not exhibit locomotor, motor coordination, repetitive, or depressive-like behaviors.
- FS-induced mice displayed increased impulsive-like behavior, more pronounced in males.
- Recurrent FS led to a higher incidence of impaired cognitive-affective transfer (CAT) and increased impulsivity compared to single FS.
- Dysregulated expression of impulsivity-related genes (e.g., 5-HT1A, tryptophan hydroxylase 2) was observed in FS-induced mice.
Conclusions:
- Male mice show higher susceptibility to behavioral consequences following FS induction than females.
- Recurrent FS increases the risk of subsequent disorders characterized by decreased anxiety and heightened impulsivity.
- The serotonin system is implicated as a potential mechanism underlying increased impulsivity after FS.
Abstract:
Febrile seizure (FS) is one of the most prevalent etiological events in childhood affecting 2-5% of children from 3 months to 5 years old. Debates on whether neurodevelopmental consequences rise in later life following a febrile seizure or not are still ongoing however there is limited evidence of its effect, especially in a laboratory setting. Moreover, the comparative study using both male and female animal models is sparse. To examine the effect of FS on the behavioral features of mice, both sexes of ICR mice were induced with hyperthermic seizures through exposure to an infrared heat lamp. The mice were divided into two groups, one receiving a single febrile seizure at postnatal day 11 (P11) and one receiving three FS at P11, P13, and P15. Starting at P30 the FS-induced mice were subjected to a series of behavioral tests. Mice with seizures showed no locomotor and motor coordination deficits, repetitive, and depressive-like behavior. However, the FS-induced mice showed impulsive-like behavior in both elevated plus maze and cliff avoidance tests, which is more prominent in male mice. A greater number of mice displayed impaired CAT in both males and females in the three-time FS-induced group compared to the single induction group. These results demonstrate that after induction of FS, male mice have a higher susceptibility to consequences of febrile seizure than female mice and recurrent febrile seizure has a higher chance of subsequent disorders associated with decreased anxiety and increased impulsivity. We confirmed the dysregulated expression of impulsivity-related genes such as 5-HT1A and tryptophan hydroxylase 2 from the prefrontal cortices of FS-induced mice implying that the 5-HT system would be one of the mechanisms underlying the increased impulsivity after FS. Taken together, these findings are useful in unveiling future discoveries about the effect of childhood febrile seizure and the mechanism behind it.
