Dissecting neural circuit deficits in an animal model of Dravet syndrome
The goal of this project is to generate transgenic animals to identify neural deficits in an animal model of the Dravet syndrome (https:// no.wikipedia.org/wiki/Dravets_syndrom). The Dravet syndrome represents a severe form of human epilepsy caused by deficits of the scn1a gene. The scn1a gene encodes voltage-gated Na+ channels that are expressed in inhibitory nerve cells in the brain. We hypothesize that scn1a gene deficits will damage nerve cells that generate inhibition in the central nervous system. When inhibition is impaired, excitation takes over, causing epilepsy and a broad range of brain disorders.
To reach the goal of the project, we will use our high expertise in cellular and subcellular in vitro electrophysiology to study neural deficits in a mouse model of the Dravet syndrome (available from the Jackson Laboratory, https://www.jax.org/strain/024761). To maximally support animal welfare in biomedical research, we will use a transgenic approach that creates heterozygous mice with an intermediate disease phenotype. We plan to use up to 150 scn1a-deficient mice (scn1a+/-) of either sex at the age between 17 to 35 days, around the reported seizure onset. Additionally, we will use up to 150 age-matched wild-type littermates as controls. Animals will only be used for in vitro experiments under the guideline of the Norwegian Food Safety Authority. We will use the results obtained from in vitro experiments to construct a computer model for simulating neural circuit dysfunctions in the Dravet syndrome. A long-term vision of this project is to use the obtained results for building a full in silico digital approach, where computer modeling techniques are used to replace, reduce and refine the use of animal in the research of human diseases.
To reach the goal of the project, we will use our high expertise in cellular and subcellular in vitro electrophysiology to study neural deficits in a mouse model of the Dravet syndrome (available from the Jackson Laboratory, https://www.jax.org/strain/024761). To maximally support animal welfare in biomedical research, we will use a transgenic approach that creates heterozygous mice with an intermediate disease phenotype. We plan to use up to 150 scn1a-deficient mice (scn1a+/-) of either sex at the age between 17 to 35 days, around the reported seizure onset. Additionally, we will use up to 150 age-matched wild-type littermates as controls. Animals will only be used for in vitro experiments under the guideline of the Norwegian Food Safety Authority. We will use the results obtained from in vitro experiments to construct a computer model for simulating neural circuit dysfunctions in the Dravet syndrome. A long-term vision of this project is to use the obtained results for building a full in silico digital approach, where computer modeling techniques are used to replace, reduce and refine the use of animal in the research of human diseases.