Signalling pathways contributing to learning and memory deficits in the Ts65Dn mouse model of Down syndrome.

Abstract

Down syndrome (DS) is a genetic trisomic disorder that produces life-long changes in physiology and cognition. Many of the changes in learning and memory seen in DS are reminiscent of disorders involving the hippocampal/entorhinal circuit. Mouse models of DS typically involve trisomy of murine chromosome 16 is homologous for many of the genes triplicated in human trisomy 21, and provide us with good models of changes in, and potential pharmacotherapy for, human DS. Recent careful dissection of the Ts65Dn mouse model of DS has revealed differences in key signalling pathways from the basal forebrain to the hippocampus and associated rhinal cortices, as well as changes in the microstructure of the hippocampus itself. In vivo behavioural and electrophysiological studies have shown that Ts65Dn animals have difficulties in spatial memory that mirror hippocampal deficits, and have changes in hippocampal electrophysiological phenomenology that may explain these differences, and align with expectations generated from in vitro exploration of this model. Finally, given the existing data, we will examine the possibility for pharmacotherapy for DS, and outline the work that remains to be done to fully understand this system.