Optogenetic control of epileptiform activity.
Författare
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.
Publiceringsår
2009
Språk
Engelska
Sidor
12162-12167
Publikation/Tidskrift/Serie
Proceedings of the National Academy of Sciences
Volym
106
Issue
29
Länkar
Dokumenttyp
Artikel i tidskrift
Förlag
National Academy of Sciences
Ämne
- Neurosciences
- Neurology
Nyckelord
- NpHR
- paroxysmal depolarizing shift (PDS)
- epilepsy
- hippocampus
- stimulation train-induced bursting (STIB)
Status
Published
Forskningsgrupp
- CNS Gene Therapy
- Experimental Epilepsy Group
ISBN/ISSN/Övrigt
- ISSN: 1091-6490