The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

Optogenetic control of epileptiform activity.

På svenska

Author

Summary, in English

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.

Publishing year

2009

Language

English

Pages

12162-12167

Publication/Series

Proceedings of the National Academy of Sciences

Volume

106

Issue

29

Document type

Journal article

Publisher

National Academy of Sciences

Topic

  • Neurosciences
  • Neurology

Keywords

  • NpHR
  • paroxysmal depolarizing shift (PDS)
  • epilepsy
  • hippocampus
  • stimulation train-induced bursting (STIB)

Status

Published

Research group

  • CNS Gene Therapy
  • Experimental Epilepsy Group

ISBN/ISSN/Other

  • ISSN: 1091-6490