Online Archive of University of Virginia Scholarship
Untangling the nets: Perineuronal net remodeling in pilocarpine-induced status epilepticus87 views
Author
Woo, AnnaLin, Neuroscience - School of Medicine, University of Virginia0000-0003-3552-8692
Advisors
Sontheimer, Harald, MD-NESC Neuroscience, University of Virginia
Abstract
Epilepsy is a chronic disease defined by spontaneous recurrent seizures, believed to be due to excitation-inhibition imbalances. Irregular neuronal activity is often associated with other cellular and molecular aberrations including neurodegeneration, astrogliosis, and malfunction of inhibitory interneurons. Increasing evidence points towards alterations in the extracellular matrix (ECM) as being associated with acquired epilepsy in both human patients and experimental models. Highly condensed structures of the ECM called perineuronal nets (PNNs) are particularly implicated, primarily due to their formation around inhibitory fast-spiking interneurons and research suggesting that they are key to the normal functioning of these cells.
The work in this dissertation investigates the role of ECM in a mouse model of temporal lobe epilepsy (TLE). Using molecular, electrophysiological, and transcriptomic techniques, we explore novel PNNs that develop in the CA1 region of the hippocampus following onset of status epilepticus (SE). We demonstrate increased excitability in the cells that acquire these PNNs, and identify the cells as a mixed population of interneurons, with partial but not complete rescue of excitability upon PNN degradation. Bulk RNA sequencing experiments reveal transcriptome changes associated with ECM remodeling and inflammation related genes.
Altogether, this work provides insights into the role of PNNs in epileptogenesis, specifically with regards to altered interneuron excitability. These insights suggest potential mechanisms underlying epileptogenesis, and implicate ECM and PNN-related pathways and molecules as possible targets for therapeutic interventions and developments.
Woo, AnnaLin. Untangling the nets: Perineuronal net remodeling in pilocarpine-induced status epilepticus. University of Virginia, Neuroscience - School of Medicine, PHD (Doctor of Philosophy), 2025-07-14, https://doi.org/10.18130/za4j-6r54.
