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bioRxiv · 10.1101/2025.04.15.649044

Single electrically induced epileptic afterdischarge triggers synaptic weakening, AMPA receptor endocytosis and shrinkage of dendritic spines in the hippocampus

Crestani, A. P.·Zacharias, L. R.·Marques, D. B.·Fonseca, F. F. F.·Ruggiero, R. N.·Leite, J. P.
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Abstract

Afterdischarge (AD) is an experimental model of electrically induced seizures. When induced in limbic structures, AD is known to induce acute behavioral alterations and flattening of local field potentials that persist for a few minutes. However, impairments in more complex cognitive processes such as learning and memory, can last for hours after the seizure. Considering the mismatch between ephemeral postictal electrophysiological changes and long-lasting cognitive impairments, synaptic plasticity emerges as a possible mechanism that integrates these findings. Therefore, we used a multilevel approach to evaluate the effects of a single seizure on synaptic plasticity. First, we showed that a single AD-eliciting stimulation at the perforant pathway-dentate gyrus (PP-DG) synapse causes long-lasting decrease of evoked postsynaptic potentials. Then, we observed that this functional alteration was accompanied by shrinkage of mushroom-shaped spines in the DG. Lastly, reduced levels of p(Ser845)-GluA1 and GluA1 subunits of AMPA receptors (AMPARs) were found in the hippocampal postsynaptic density. Together, our data suggest that a seizure induces a long-term depression (LTD)-like synaptic plasticity phenomenon, which is characterized by synaptic weakening, AMPAR endocytosis, and dendritic spines shrinkage. Furthermore, the postictal changes in synaptic plasticity observed here align with the course of cognitive impairments often reported in other studies.

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Crestani, A. P., Zacharias, L. R., Marques, D. B., Fonseca, F. F. F., Ruggiero, R. N., Leite, J. P.. 2025-04-20. Single electrically induced epileptic afterdischarge triggers synaptic weakening, AMPA receptor endocytosis and shrinkage of dendritic spines in the hippocampus. https://doi.org/10.1101/2025.04.15.649044

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