Size Does Not Always Matter: Ts65Dn Down Syndrome Mice Show Cerebellum-Dependent Motor Learning Deficits that Cannot Be Rescued by Postnatal SAG Treatment

• DOI: 10.1523/jneurosci.2198-13.2013
• Publication Date: 2013-09-25T16:47:08Z
• Authors: Nicolas Gutierrez...; Beerend H.J. Wink...; Leonardo Tolosa-R...; Benjamin Devenney; Roger H. Reeves; Chris I. De Zeeuw
• Keywords: Cerebellar hemisphere

Humans with Down syndrome (DS) and Ts65Dn mice both show a reduced volume of the cerebellum due to significant reduction in density granule neurons. Recently, cerebellar hypoplasia was rescued by single treatment SAG, an agonist Sonic hedgehog pathway, administered on day birth. In addition normalizing morphology, this restored ability learn spatial navigation task, which is associated hippocampal function. It not clear what extent improved performance results from restoration architecture or yet undefined role (Shh) perinatal development. The absence clearly demonstrated deficit function trisomic exacerbates problem discerning how SAG acts improve learning memory. Here we that phase reversal adaptation consolidation vestibulo-ocular reflex significantly impaired mice, providing for first time precise characterization functional deficits murine model DS. However, these do benefit normalization morphology following SAG. Together previous observation synaptic properties Purkinje cells are also unchanged treatment, lack improvement region-specific behavioral assay supports possibility direct effect Shh pathway stimulation hippocampus might explain benefits potential approach cognition