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Manganese-enhanced magnetic resonance imaging (MEMRI) exploits the biophysical similarity of Ca 2+ and Mn 2+ to map the brain's activity in vivo . However, to what extent different Ca 2+ channels contribute to the enhanced signal that MEMRI provides and how Mn 2+ dynamics influence Mn 2+ brain accumulation after systemic administration of MnCl 2 are not yet fully understood. Here, we demonstrate that mice lacking the L-type Ca 2+ channel 1.2 (Ca v 1.2) in the CNS show approximately 50% less increase in MEMRI contrast after repeated systemic MnCl 2 injections, as compared to control mice. In contrast, genetic deletion of L-type Ca 2+ channel 1.3 (Ca v 1.3) did not reduce signal. Brain structure- or cell type-specific deletion of Ca v 1.2 in combination with voxel-wise MEMRI analysis revealed a preferential accumulation of Mn 2+ in projection terminals, which was confirmed by local MnCl 2 administration to defined brain areas. Taken together, we provide unequivocal evidence that Ca v 1.2 represents an important channel for neuronal Mn 2+ influx after systemic injections. We also show that after neuronal uptake, Mn 2+ preferentially accumulates in projection terminals. [ABSTRACT FROM AUTHOR]