Activity-dependent volume transmission by transgene NPY attenuates glutamate release and LTP in subiculum

Research output: Contribution to journalArticle

Abstract

Neuropeptide Y (NPY) gene transduction of the brain using viral vectors in epileptogenic regions can effectively suppress seizures in animals, and is being considered as a promising alternative treatment strategy for epilepsy. Therefore, it is fundamental to understand the detailed mechanisms governing the release and action of transgene NPY in neuronal circuitries. Using whole-cell recordings from subicular neurons, we show that in animals transduced by recombinant adeno-associated viral (rAAV) vector carrying the NPY gene, transgene NPY is released during high-frequency activation of CA1-subicular synapses. Released transgene NPY attenuates excitatory synaptic transmission not only in activated, but also in neighboring, non-activated synapses. Such broad action of transgene NPY may prevent recruitment of excitatory synapses in epileptic activity and could play a key role in limiting the spread and generalization of seizures.

Details

Authors
  • Andreas Toft Sörensen
  • Irene Kanter Schlifke
  • En-Ju D. Lin
  • Matthew J. During
  • Merab Kokaia
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurology

Keywords

  • Long-term potentiation (LTP), Activity-dependent release, Synaptic transmission, Synaptic plasticity, Neuropeptide Y, Gene therapy, Whole-cell patch-clamp, Subiculum
Original languageEnglish
Pages (from-to)229-37
JournalMolecular and Cellular Neuroscience
Volume39
Issue number2
Publication statusPublished - 2008
Publication categoryResearch
Peer-reviewedYes

Related research output

Toft Sörensen, A., 2008, Institutionen för kliniska vetenskaper, Lunds universitet. 134 p.

Research output: ThesisDoctoral Thesis (compilation)

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