Marco Capogna

Human limbic encephalitis serum enhances hippocampal mossy fiber-CA3 pyramidal cell synaptic transmission

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Tatjana Lalic, MRC Anatomical Neuropharmacology Unit, Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3TH, UK. Electronic address: marco.capogna@pharm.ox.ac.uk.
  • ,
  • Philippa Pettingill
  • ,
  • Angela Vincent
  • ,
  • Marco Capogna

PURPOSE: Limbic encephalitis (LE) is a central nervous system (CNS) disease characterized by subacute onset of memory loss and epileptic seizures. A well-recognized form of LE is associated with voltage-gated potassium channel complex antibodies (VGKC-Abs) in the patients' sera. We aimed to test the hypothesis that purified immunoglobulin G (IgG) from a VGKC-Ab LE serum would excite hippocampal CA3 pyramidal cells by reducing VGKC function at mossy-fiber (MF)-CA3 pyramidal cell synapses.

METHODS: We compared the effects of LE and healthy control IgG by whole-cell patch-clamp and extracellular recordings from CA3 pyramidal cells of rat hippocampal acute slices.

RESULTS: We found that the LE IgG induced epileptiform activity at a population level, since synaptic stimulation elicited multiple population spikes extracellularly recorded in the CA3 area. Moreover, the LE IgG increased the rate of tonic firing and strengthened the MF-evoked synaptic responses. The synaptic failure of evoked excitatory postsynaptic currents (EPSCs) was significantly lower in the presence of the LE IgG compared to the control IgG. This suggests that the LE IgG increased the release probability on MF-CA3 pyramidal cell synapses compared to the control IgG. Interestingly, α-dendrotoxin (120 nm), a selective Kv1.1, 1.2, and 1.6 subunit antagonist of VGKC, mimicked the LE IgG-mediated effects.

CONCLUSIONS: This is the first functional demonstration that LE IgGs reduce VGKC function at CNS synapses and increase cell excitability.

Original languageEnglish
JournalEpilepsia
Volume52
Issue1
Pages (from-to)121-31
Number of pages11
ISSN0013-9580
DOIs
Publication statusPublished - Jan 2011

Bibliographical note

Wiley Periodicals, Inc. © 2010 International League Against Epilepsy.

    Research areas

  • Animals, CA3 Region, Hippocampal/physiology, Humans, Immunoglobulin G/administration & dosage, Limbic Encephalitis/blood, Male, Middle Aged, Mossy Fibers, Hippocampal/physiology, Organ Culture Techniques, Pyramidal Cells/physiology, Rats, Rats, Sprague-Dawley, Synaptic Transmission/physiology

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