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 Mn^(2+) enhanced 3D MRI and compare normal with a trisomic mouse model of DS, Ts65Dn. After injection of 4 nl of 200 mM Mn^(2+) into the right hippocampus, Mn^(2+) 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 Mn^(2+) 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.
Additional Information© 2007 Elsevier Inc. Received 8 February 2007; revised 11 April 2007; accepted 2 May 2007. Available online 18 May 2007. We thank Muriel Davisson and Cecilia Schmidt for their advice and help in obtaining and genotyping aged Ts65Dn mice and 2N littermates, to J.D. DelCroix for advice on hippocampal injections, and to the Moore Foundation for the Moore Distinguished Scholar award that brought E.L.B. to Caltech to collaborate in this work. The project was in part funded by NINDS NS046810, NIGMS GM47368 (E.L.B.), NCRR U24 RR021760 entitled Mouse BIRN and NIDA R01DA018184 (R.E.J.).
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