Live imaging of neuronal connections by magnetic resonance: Robust transport in the hippocampal-septal memory circuit in a mouse model of Down syndrome

Connections from hippocampus to septal nuclei have been implicated in memory loss and the cognitive impairment in Down syndrome (DS). We trace these connections in living mice by Mn2+ enhanced 3D MRI and compare normal with a trisomic mouse model of DS, Ts65Dn. After injection of 4 nl of 200 mM Mn2+ into the right hippocampus, Mn2+ enhanced circuitry was imaged at 0.5, 6, and 24 h in each of 13 different mice by high resolution MRI to detect dynamic changes in signal over time. The pattern of Mn2+ enhanced signal in vivo correlated with the histologic pattern in fixed brains of co-injected 3kD rhodamine-dextran-amine, a classic tracer. Statistical parametric mapping comparing intensity changes between different time points revealed that the dynamics of Mn2+ transport in this pathway were surprisingly more robust in DS mice than in littermate controls, with statistically significant intensity changes in DS appearing at earlier time points along expected pathways. This supports reciprocal alterations of transport in the hippocampal-forebrain circuit as being implicated in DS and argues against a general failure of transport. This is the first examination of in vivo transport dynamics in this pathway and the first report of elevated transport in DS.