Seizure-induced strengthening of a recurrent excitatory circuit in the dentate gyrus is proconvulsant
Abstract
Better understanding of the initial molecular and cellular processes implicated in epileptogenesis is essential for early therapeutic intervention (i.e., before brain damage becomes irreversible). Uncontrolled activity of recurrent excitatory circuits is a common mechanism that promotes epileptic activity. In the dentate gyrus, mossy and granule cells form a recurrent excitatory circuit that can be strengthened upon activity and whose dysregulation has been implicated in temporal lobe epilepsy. Here, we found that acute induction of seizures triggers robust brain-derived neurotrophic factor (BDNF)-dependent strengthening of mossy cell-granule cell synapses that promotes further convulsive seizures. Moreover, blocking this synaptic strengthening prevents seizure activity. Together, our findings provide a potential mechanism for early epileptogenesis involving BDNF within a recurrent hippocampal excitatory network.
- Publication:
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Proceedings of the National Academy of Science
- Pub Date:
- August 2022
- DOI:
- 10.1073/pnas.2201151119
- Bibcode:
- 2022PNAS..11901151N