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Updated: Nov 5, 2025
Assessment of Dendritic Arborization in the Dentate Gyrus of the Hippocampal Region in Mice
Published on: March 31, 2015
Altered hippocampal dendritic spine maturation after hypoxia-induced seizures in neonatal rats
Jocelyn J Lippman-Bell1, Marcus Handy2, Cassidy G Nieder3
1Department of Biomedical Sciences, Philadelphia College of Osteopathic Medicine, Philadelphia, PA, United States of America; Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States of America.
Insights
Early-life seizures disrupt normal brain development, leading to immature synapses and cognitive issues. This study reveals impaired dendritic spine maturation after seizures, potentially explaining long-term neurodevelopmental deficits.
Area of Science:
- Neuroscience
- Developmental Biology
- Synaptic Plasticity
Background:
- Cognitive comorbidities are common after early-life seizures (ELS), particularly in neurodevelopmental disorders.
- The impact of ELS on neuronal and synaptic development remains incompletely understood.
- Previous work showed hypoxia-induced seizures (HS) in rats impair cognition and alter hippocampal neurotransmission.
Purpose of the Study:
- To investigate whether ELS induce developmentally specific changes in dendritic spine maturation.
- To determine if impaired spine maturation contributes to cognitive deficits following ELS.
- To explore the molecular mechanisms underlying altered synaptic development post-ELS.
Main Methods:
- Hypoxia-induced seizures (HS) were induced in postnatal day 10 (P10) rats.
- Dendritic spine development was assessed in hippocampal CA1 pyramidal neurons at various intervals up to P38.
- Synaptic maturation markers (PSD-95) and actin-regulating proteins (cofilin) were analyzed.
Main Results:
- Post-seizure rats exhibited a failure to decrease dendritic spine density from P10 to P38, unlike controls.
- Spines in post-seizure rats appeared more immature (long, thin) and had increased PSD-95 expression.
- A transient increase in phosphorylated cofilin indicated reduced cofilin activity, preceding spine changes.
Conclusions:
- ELS impair normal dendritic spine maturation and pruning in the developing hippocampus.
- This results in an excess of immature, less efficient synapses, potentially via altered actin dynamics.
- Deficits in structural plasticity following ELS may underlie later-life cognitive consequences and neurodevelopmental disorders.
Abstract:
Cognitive comorbidities often follow early-life seizures (ELS), especially in the setting of autism and other neurodevelopmental syndromes. However, there is an incomplete understanding of whether neuronal and synaptic development are concomitantly dysregulated. We have previously shown that hypoxia-induced seizures (HS) in postnatal day (P)10 rats increase acute and later-life hippocampal glutamatergic neurotransmission and spontaneous recurrent seizures, and impair cognition and behavior. As dendritic spines critically regulate synaptic function, we hypothesized that ELS can induce developmentally specific changes in dendritic spine maturation. At intervals during one month following HS in P10 rats, we assessed dendritic spine development on pyramidal neurons in the stratum radiatum of hippocampal area CA1. Compared to control rats in which spine density significantly decreased from P10 to early adulthood (P38), post-seizure rats failed to show a developmental decrease in spine density, and spines from P38 post-seizure rats appeared more immature-shaped (long, thin). In addition, compared to P38 control rats, post-seizure P38 rats expressed significantly more synaptic PSD-95, a marker of mature synapses. These changes were preceded by a transient increase in hippocampal expression of cofilin phosphorylated at Ser3, representing a decrease in cofilin activity. These results suggest that early-life seizures may impair normal dendritic spine maturation and pruning in CA1 during development, resulting in an excess of less efficient synapses, via activity-dependent modification of actin-regulating proteins such as cofilin. Given that multiple neurodevelopmental disorders show similar failures in developmental spine pruning, the current findings may represent a deficit in structural plasticity that could be a component of a mechanism leading to later-life cognitive consequences associated with early-life seizures.
