Impairment of GABA release in the hippocampus at the time of the first spontaneous seizure in the pilocarpine model of temporal lobe epilepsy

Marie Soukupová, Anna Binaschi, Chiara Falcicchia, Silvia Zucchini, Paolo Roncon, Eleonora Palma, Eros Magri, Enrico Grandi, Michele Simonato

Research output: Contribution to journalArticlepeer-review

Abstract

The alterations in GABA release have not yet been systematically measured along the natural course of temporal lobe epilepsy. In this work, we analyzed GABA extracellular concentrations (using in vivo microdialysis under basal and high K+-evoked conditions) and loss of two GABA interneuron populations (parvalbumin and somatostatin neurons) in the ventral hippocampus at different time-points after pilocarpine-induced status epilepticus in the rat, i.e. during development and progression of epilepsy. We found that (i) during the latent period between the epileptogenic insult, status epilepticus, and the first spontaneous seizure, basal GABA outflow was reduced to about one third of control values while the number of parvalbumin-positive cells was reduced by about 50% and that of somatostatin-positive cells by about 25%; nonetheless, high K+ stimulation increased extracellular GABA in a proportionally greater manner during latency than under control conditions; (ii) at the time of the first spontaneous seizure (i.e., when the diagnosis of epilepsy is made in humans) this increased responsiveness to stimulation disappeared, i.e. there was no longer any compensation for GABA cell loss; (iii) thereafter, this dysfunction remained constant until a late phase of the disease. These data suggest that a GABAergic hyper-responsiveness can compensate for GABA cell loss and protect from occurrence of seizures during latency, whereas impaired extracellular GABA levels can favor the occurrence of spontaneous recurrent seizures and the maintenance of an epileptic state.

Original languageEnglish
Pages (from-to)39-49
Number of pages11
JournalExperimental Neurology
Volume257
DOIs
Publication statusPublished - 2014

Keywords

  • GABA release
  • Parvalbumin
  • Pilocarpine
  • Somatostatin
  • Temporal lobe epilepsy

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

Fingerprint Dive into the research topics of 'Impairment of GABA release in the hippocampus at the time of the first spontaneous seizure in the pilocarpine model of temporal lobe epilepsy'. Together they form a unique fingerprint.

Cite this