Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • News & Views
  • Published:

Intracellular chloride accumulation: a possible mechanism for cognitive deficits in Down syndrome

A study involving a mouse model of Down syndrome and analysis of human postmortem brain samples indicates that hippocampal GABAA receptor signaling in Down syndrome may be excitatory. This advance promises new clinical applications in Down syndrome.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Schematic model of GABAA receptor–mediated neurotransmission in a mouse model of DS.

Kim Caesar/Nature Publishing Group


  1. Lejeune, J. et al. Ann. Genet. 1, 1–49 (1959).

    Google Scholar 

  2. Patterson, D. & Costa, A.C. Nat. Rev. Genet. 6, 137–147 (2005).

    Article  CAS  Google Scholar 

  3. Parker, S.E. et al. Birth Defects Res. A Clin. Mol. Teratol. 88, 1008–1016 (2010).

    Article  CAS  Google Scholar 

  4. Nadel, L. Genes Brain Behav. 2, 156–166 (2003).

    Article  CAS  Google Scholar 

  5. Zigman, W.B. & Lott, I.T. Ment. Retard. Dev. Disabil. Res. Rev. 13, 237–246 (2007).

    Article  Google Scholar 

  6. Deidda, G. et al. Nat. Med. 21, 318–326 (2015).

    Article  CAS  Google Scholar 

  7. Fernandez, F. et al. Nat. Neurosci. 10, 411–413 (2007).

    Article  CAS  Google Scholar 

  8. Costa, A.C. & Scott-McKean, J.J. CNS Drugs 27, 679–702 (2013).

    Article  CAS  Google Scholar 

  9. Dzhala, V.I. et al. Nat. Med. 11, 1205–1213 (2005).

    Article  CAS  Google Scholar 

  10. Puskarjov, M. et al. Epilepsia 55, 806–818 (2014).

    Article  CAS  Google Scholar 

  11. Töpfer, M. Eur. J. Neurosci. 39, 673–687 (2014).

    Article  Google Scholar 

  12. Krystal, A.D. et al. PLoS ONE 7, e35417 (2012).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations


Corresponding author

Correspondence to Alberto C Costa.

Ethics declarations

Competing interests

The author declares no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Costa, A. Intracellular chloride accumulation: a possible mechanism for cognitive deficits in Down syndrome. Nat Med 21, 312–313 (2015).

Download citation

  • Published:

  • Issue Date:

  • DOI:

This article is cited by


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing