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Updated: Mar 23, 2026
A Behavioral Screen for Heat-Induced Seizures in Mouse Models of Epilepsy
Published on: July 12, 2021
Experimental febrile seizures increase dendritic complexity of newborn dentate granule cells
Marjolein Raijmakers1,2, Elke Clynen1, Nick Smisdom1,3
1Biomedical Research Institute BIOMED, Hasselt University, Hasselt, Belgium.
Insights
Febrile seizures (FS) in young rats promote lasting changes in newborn neurons within the hippocampus. These neurons exhibit enhanced dendritic complexity and a more mature structure, potentially altering brain network function.
Area of Science:
- Neuroscience
- Developmental Biology
- Epilepsy Research
Background:
- Febrile seizures (FS) are common in early childhood and can lead to epilepsy.
- Hippocampal excitability, regulated by the dentate gyrus (DG) and its neurogenesis, is implicated in epilepsy.
- The long-term impact of FS on newly generated hippocampal neurons remains unclear.
Purpose of the Study:
- To investigate the temporal maturation and structural integration of dentate granule cells (DGCs) born after experimental FS.
- To understand how FS influences the development of new neurons in the hippocampus.
Main Methods:
- Experimental FS were induced in 10-day-old rat pups.
- Newborn cells in the DG were labeled with enhanced green fluorescent protein (eGFP) via retroviral injection.
- Histochemical analyses assessed neurodevelopmental markers, dendritic complexity, and spine density/morphology at 1, 4, and 8 weeks post-injection.
Main Results:
- No significant differences in neurodevelopmental markers were observed between FS and control groups.
- DGCs in FS animals exhibited significantly longer dendrites (66% at 1 week) and increased dendritic intersections (20-25% at 4-8 weeks).
- An increase in mushroom-type spines was noted in FS animals after 8 weeks, suggesting enhanced excitatory input.
Conclusions:
- Experimental FS enhance the dendritic complexity and promote a more mature phenotype in newly generated DGCs.
- These structural changes suggest increased excitatory information processing in the DG following FS.
- Further research is needed to determine the functional consequences of this enhanced connectivity on hippocampal signaling.
Objective:
Febrile seizures (FS) are fever-associated convulsions, being the most common seizure disorder in early childhood. A subgroup of these children later develops epilepsy characterized by a hyperexcitable neuronal network in the hippocampus. Hippocampal excitability is regulated by the hippocampal dentate gyrus (DG) where postnatal neurogenesis occurs. Experimental FS increase the survival of newborn hippocampal dentate granule cells (DGCs), yet the significance of this neuronal subpopulation to the hippocampal network remains unclear. In the current study, we characterized the temporal maturation and structural integration of these post-FS born DGCs in the DG.
Methods:
Experimental FS were induced in 10-day-old rat pups. The next day, retroviral particles coding for enhanced green fluorescent protein (eGFP) were stereotactically injected in the DG to label newborn cells. Histochemical analyses of eGFP expressing DGCs were performed one, 4, and 8 weeks later and consisted of the following: (1) colocalization with neurodevelopmental markers doublecortin, calretinin, and the mature neuronal marker NeuN; (2) quantification of dendritic complexity; and (3) quantification of spine density and morphology.
Results:
At neither time point were neurodevelopmental markers differently expressed between FS animals and normothermia (NT) controls. One week after treatment, DGCs from FS animals showed dendrites that were 66% longer than those from NT controls. At 4 and 8 weeks, Sholl analysis of the outer 83% of the molecular layer showed 20-25% more intersections in FS animals than in NT controls (p < 0.01). Although overall spine density was not affected, an increase in mushroom-type spines was observed after 8 weeks.
Significance:
Experimental FS increase dendritic complexity and the number of mushroom-type spines in post-FS born DGCs, demonstrating a more mature phenotype and suggesting increased incoming excitatory information. The consequences of this hyperconnectivity to signal processing in the DG and the output of the hippocampus remain to be studied.
