In vivo tracing of major rat brain pathways using manganese-enhanced magnetic resonance imaging and three-dimensional digital atlasing

The magnetic resonance imaging (MRI)-detectable T1 contrast agent manganese (Mn2+) has recently been introduced as a neural tracer in rodents, birds, and monkeys. We have tested to what extent this in vivo method is useful for three-dimensional (3-D) survey of connectivity patterns in the rat somatosensory system. A commonly available 3 T human clinical MRI scanner was used to trace neural pathways following focal injection of manganese chloride (MnCl2) in the somatosensory cortex. Six to 10 h after MnCl2 injection, we found significant signal enhancement in major projection systems, including corticocortical, corticostriatal, corticothalamic, corticotectal, corticopontine, and corticospinal pathways. To facilitate the assignment of anatomic localization to the observed Mn2+ signal enhancement, we registered the MRI data with a 3-D digital reconstruction of a stereotaxic rat brain atlas. Across-animal comparison using the digital model allowed demonstration of a corticothalamic 3-D topographic organization in agreement with previously published two-dimensional topographic schemes based on classical neural tracing data. We conclude that anterograde MnCl2/MRI tracing allows rapid analysis of topographic organization across multiple brain regions. The method allows a higher data throughput for 3-D studies of large-scale brain connectivity than conventional methods based on tissue sectioning.