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Free keywords:
IN-VIVO; CALCIUM-CHANNELS; HIPPOCAMPAL-NEURONS; REPORTER PROTEIN; BRAIN
ACTIVATION; RAT HIPPOCAMPUS; CA2+ CHANNELS; MICE; MOUSE; NEUROTOXICITYNeurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging; Manganese enhanced MRI; Functional imaging; Connectomics;
Activity-dependent; CACNA1C; Calcium channels;
Abstract:
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 (Ca(v)1.2) 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 (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 Mn2+ in projection terminals, which was confirmed by local MnCl2 administration to defined brain areas.
Taken together, we provide unequivocal evidence that Ca(v)1.2 represents an important channel for neuronal Mn2+ influx after systemic injections. We also show that after neuronal uptake, Mn2+ preferentially accumulates in projection terminals.
