Abstract Manganese (Mn2+) is an essential element for human body. The paramagnetic properties of Mn2+ permit it use as a contrast agent for MRI (Mn-MRI or MEMRI). Analogue of calcium (Ca2+), it enters neurons primarily by calcium channels. It is then transported along microtubules to the synapse where it is released and then captured by other neurons. Thus, it can account for the anterograde and retrograde axonal transport. The MEMRI approach can provide unique information about cerebral functional connectivity. Two problems limit the use of this powerful tool for in vivo imaging: (i) At high doses, Mn2+ is toxic to the body and can cause serious problem of the central nervous system, called manganism. The level and the mechanisms of toxicity are poorly understood. (ii) The mode of manganese transport in the MEMRI approach is unclear. To address these two issues, we undertook a study coupling MRI and synchrotron microscopy to study the Mn 2+ behavior in vivo. We characterized the cellular and subcellular distributions of Mn and other metals in "pseudo neurons" cell line N2A, primary cultures of hippocampal neurons, andin hippocampal slices from rats. In parallel, we studied the effects of Mn on brain metabolism by proton-HRMAS NMR . In parallel, weevaluated MEMRI in MAP6 KO mice which exhibit a deficit in microtubule stabilizing protein, to assess the functional connectivity of the thalamocortical tract. Key words hippocampus, MAP6, manganese, metabolism, metal, neuron, MRI, rodent, synchrotron.
