Tracing neural circuits in vivo with Mn-enhanced MRI

The application of MRI-visible paramagnetic tracers to reveal in vivo connectivity can provide important subject-specific information for multisite, multielectrode intracortical recordings in combined behavioral and physiology experiments. To establish the use of such tracers in the nonhuman primate, we recently compared the specificity of the anterograde tracer Mn2+ with that of wheat-germ-agglutinin conjugated to horseradish peroxidase (WGA-HRP) in experiments tracing the neuronal connections of the basal ganglia of the monkey. It was shown that Mn2+ and WGA-HRP yield the same projection patterns and that the former tracer crosses at least two synapses, for it could be found in thalamus following injections into the striatum. Here we provide evidence that Mn2+ reaches the cortex following striatum injections and, thus, is transferred even further than previously shown. In other words, used as a paramagnetic MRI tracer, Mn2+ can permit the visualization of neural networks covering at least four processing stages. Moreover, unilateral intravitreal injections show that Mn2+ is sufficiently synapse specific to permit visualization of the lamina of the dorsal lateral geniculate nucleus (dLGN). Interestingly, the transfer rate of the substance reflected the well-known axonal size differences between the parvocellular and magnocellular layers of dLGN. After intravitreal injections, we were able to demonstrate transfer of Mn2+ into several subcortical and cortical areas, including the inferotemporal cortex. The specificity of the transsynaptic transfer of manganese that we report here indicates the value of this tracer for chronic studies of development and plasticity, as well as for studies of brain pathology.