A transient developmental window of fast-spiking interneuron dysfunction in a mouse model of Dravet syndrome

(Favero et al. 2018) Several years ago, researchers showed that Scn1a mutations in mice are primarily expressed in GABAergic interneurons, the inhibitory neurons that counteract excitatory neurons in the brain. A defect in these inhibitory neurons causes excess excitation, resulting in seizures and epilepsy in Dravet syndrome. However, that research was done primarily on brain slices from very young mice, and although most research and several other models (such as iPSCs) have supported this theory, the effects of Scn1a mutations on specific neurons throughout development has not been fully studied.

Here, the authors took brain slices from mice in several developmental stages and found that certain specific inhibitory neurons thought to be affected by Scn1a mutations were impaired most during the 2nd and 3rd week after birth. (On a very rough basis, 9 mice days are somewhat equivalent to 1 human year, so this corresponds very roughly to years 1-2 in human development.) Interestingly, they found that by 35 days after birth, the affected interneurons’ excitability had stabilized to normal levels. Because of this normalization, the authors suggest that the this particular interneuron dsyfunction may contribute to the development of epilepsy, but may not be the root of the long-term, chronic epilepsy in Dravet syndrome.

Favero M, Sotuyo NP, Lopez E, Kearney JA, Goldberg EM. A transient developmental window of fast-spiking interneuron dysfunction in a mouse model of Dravet syndrome. J Neurosci. 2018 Aug 13. pii: 0193-18. doi: 10.1523/JNEUROSCI.0193-18.2018. [Epub ahead of print] PubMed PMID: 30104343.
By |2018-08-15T11:24:21+00:00August 15th, 2018|Categories: DSF Research Review|Tags: , , |

About the Author:

Nicole is a former scientist and science educator who has an 11 year old son with Dravet syndrome and serves on the Board of Directors for the Dravet Syndrome Foundation. She reviews and summarizes research articles, making the content more accessible to those not involved in the scientific community.