Mn2+ dynamics in manganese-enhanced MRI (MEMRI): Cav1.2 channel-mediated uptake and preferential accumulation in projection terminals

Publication date: 1 April 2018
Source:NeuroImage, Volume 169
Author(s): Benedikt T. Bedenk, Suellen Almeida-Corrêa, Angela Jurik, Nina Dedic, Barbara Grünecker, Andreas J. Genewsky, Sebastian F. Kaltwasser, Caitlin J. Riebe, Jan M. Deussing, Michael Czisch, Carsten T. Wotjak
Manganese-enhanced magnetic resonance imaging (MEMRI) exploits the biophysical similarity of Ca²⁺ and Mn²⁺ to map the brain's activity in vivo. However, to what extent different Ca²⁺ channels contribute to the enhanced signal that MEMRI provides and how Mn²⁺ dynamics influence Mn²⁺ brain accumulation after systemic administration of MnCl2 are not yet fully understood. Here, we demonstrate that mice lacking the L-type Ca²⁺ channel 1.2 (Cav1.2) in the CNS show approximately 50% less increase in MEMRI contrast after repeated systemic MnCl2 injections, as compared to control mice. In contrast, genetic deletion of L-type Ca²⁺ channel 1.3 (Cav1.3) did not reduce signal. Brain structure- or cell type-specific deletion of Cav1.2 in combination with voxel-wise MEMRI analysis revealed a preferential accumulation of Mn²⁺ in projection terminals, which was confirmed by local MnCl2 administration to defined brain areas.Taken together, we provide unequivocal evidence that Cav1.2 represents an important channel for neuronal Mn²⁺ influx after systemic injections. We also show that after neuronal uptake, Mn²⁺ preferentially accumulates in projection terminals.

Graphical abstract

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