Long-lasting correction of in vivo LTP and cognitive deficits of mice modelling Down syndrome with an α5-selective GABAA inverse agonist.

We show for the first time in vivo LTP deficits in Ts65Dn mice. These deficits were restored for at least 6 days following acute treatment with α5IA and might be the substrate for the long-lasting pharmacological effects of α5IA on spatial working and long-term recognition and spatial memory tasks. Our results demonstrate the relevance of negative allosteric modulators of α5-containing GABAA receptors to the treatment of cognitive deficits associated with DS.