In vivo 3D MRI staining of the mouse hippocampal system using intracerebral injection of MnCl2

The morphology and function of the hippocampal system of C57BL/6J mice (n = 8) was studied in vivo using T1-weighted 3D magnetic resonance imaging (MRI) (117 mum isotropic resolution) after bilateral injection of MnCl2 (0.25 mul, 5 or 200 mM) into the posterior hippocampal formation. The neuronal uptake of the T1-shortening Mn2+ ions resulted in a pronounced MRI signal enhancement within the CA3 subfield and dentate gyros with milder increases in CA1 and subiculum. This finding is in line with differences in the excitability of hippocampal neurons previously reported using electrophysiologic recordings. The subsequent axonal transport of Mn2+ highlighted the principal extrinsic projections from the posterior hippocampal formation via the fimbria and the precommissural fornix to the dorsal part of the lateral septal nucleus. A strong MRI signal enhancement was also observed in the ventral hippocampal commissure. A timecourse analysis revealed unsaturated conditions of Mn2+ accumulation at about 2 It after injection and optimal contrast-to-noise ratios at about 6 h after injection. The present results using Mn2+ -enhanced 3D MRI open new ways for studying the role of the hippocampal system in specific aspects of learning and memory in normal and mutant mice. (C) 2004 Elsevier Inc. All rights reserved.