Excessive Inhibition

People with Down syndrome have three copies of chromosome 21 instead of two, meaning an extra copy of each of the 250 or so genes on the chromosome. Figuring out which are responsible for the various issues associated with Down syndrome is challenging. But scientists have recently determined that the gene encoding DSCAM – a cell adhesion molecule involved in neuronal circuitry – is a likely cause of at least some of the neurological symptoms. Studies in mice with simulated Down syndrome revealed an extra copy of DSCAM caused chandelier cells (like the one pictured) to develop more axons. Chandelier cells are inhibitory neurons and naturally have large numbers of axons – their branching shape giving the cell its name – but extra DSCAM caused even more axonal connections with target cells and thus greater inhibitory activity. Further work may reveal how this inhibition leads to neurological symptoms and whether it can be modulated.

Written by Ruth Williams

Ruth Williams

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Ruth is a freelance science journalist based in the US. She's a regular correspondent for The Scientist, and her work has appeared in The Lancet, Nature, Scientific American Mind, BBC Focus and elsewhere. Twitter @rooph

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• Image from work by Hao Liu, René N. Caballero-Florán and Ty Hergenreder, and colleagues
• Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA
• Image originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)
• Research published in PLOS Biology, April 2023