Journal Article

Over-expression of RCAN1 causes Down syndrome-like hippocampal deficits that alter learning and memory

Katherine R. Martin, Alicia Corlett, Daphne Dubach, Tomris Mustafa, Harold A. Coleman, Helena C. Parkington, Tobias D. Merson, James A. Bourne, Sílvia Porta, Maria L. Arbonés, David I. Finkelstein and Melanie A. Pritchard

in Human Molecular Genetics

Volume 21, issue 13, pages 3025-3041
Published in print July 2012 | ISSN: 0964-6906
Published online April 2012 | e-ISSN: 1460-2083 | DOI:
Over-expression of RCAN1 causes Down syndrome-like hippocampal deficits that alter learning and memory

Show Summary Details


People with Down syndrome (DS) exhibit abnormal brain structure. Alterations affecting neurotransmission and signalling pathways that govern brain function are also evident. A large number of genes are simultaneously expressed at abnormal levels in DS; therefore, it is a challenge to determine which gene(s) contribute to specific abnormalities, and then identify the key molecular pathways involved. We generated RCAN1-TG mice to study the consequences of RCAN1 over-expression and investigate the contribution of RCAN1 to the brain phenotype of DS. RCAN1-TG mice exhibit structural brain abnormalities in those areas affected in DS. The volume and number of neurons within the hippocampus is reduced and this correlates with a defect in adult neurogenesis. The density of dendritic spines on RCAN1-TG hippocampal pyramidal neurons is also reduced. Deficits in hippocampal-dependent learning and short- and long-term memory are accompanied by a failure to maintain long-term potentiation (LTP) in hippocampal slices. In response to LTP induction, we observed diminished calcium transients and decreased phosphorylation of CaMKII and ERK1/2—proteins that are essential for the maintenance of LTP and formation of memory. Our data strongly suggest that RCAN1 plays an important role in normal brain development and function and its up-regulation likely contributes to the neural deficits associated with DS.

Journal Article.  11287 words.  Illustrated.

Subjects: Genetics and Genomics

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.