Optogenetic control of epileptiform activity.

Research output: Contribution to journalArticle

Abstract

The optogenetic approach to gain control over neuronal excitability both in vitro and in vivo has emerged as a fascinating scientific tool to explore neuronal networks, but it also opens possibilities for developing novel treatment strategies for neurologic conditions. We have explored whether such an optogenetic approach using the light-driven halorhodopsin chloride pump from Natronomonas pharaonis (NpHR), modified for mammalian CNS expression to hyperpolarize central neurons, may inhibit excessive hyperexcitability and epileptiform activity. We show that a lentiviral vector containing the NpHR gene under the calcium/calmodulin-dependent protein kinase IIalpha promoter transduces principal cells of the hippocampus and cortex and hyperpolarizes these cells, preventing generation of action potentials and epileptiform activity during optical stimulation. This study proves a principle, that selective hyperpolarization of principal cortical neurons by NpHR is sufficient to curtail paroxysmal activity in transduced neurons and can inhibit stimulation train-induced bursting in hippocampal organotypic slice cultures, which represents a model tissue of pharmacoresistant epilepsy. This study demonstrates that the optogenetic approach may prove useful for controlling epileptiform activity and opens a future perspective to develop it into a strategy to treat epilepsy.

Details

Authors
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurosciences
  • Neurology

Keywords

  • NpHR, paroxysmal depolarizing shift (PDS), epilepsy, hippocampus, stimulation train-induced bursting (STIB)
Original languageEnglish
Pages (from-to)12162-12167
JournalProceedings of the National Academy of Sciences
Volume106
Issue number29
Publication statusPublished - 2009
Publication categoryResearch
Peer-reviewedYes

Related research output

Tönnesen, J., 2010, Lund University, Faculty of Medicine. 168 p.

Research output: ThesisDoctoral Thesis (compilation)

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