Transneuronal tracing with neurotropic viruses reveals network macroarchitecture

A major challenge in systems neuroscience is to unravel the complex matrix of connections that characterize functional circuits within the central nervous system. Retrograde transneuronal transport of rabies virus has proven to be especially useful for this purpose. Here we provide specific examples in which transneuronal transport of rabies virus has been used to unravel multi-synaptic pathways within motor, cognitive and autonomic circuits. Tracing with rabies virus defined: first, the closed-loop organization of cerebellar and basal ganglia circuits with the cerebral cortex; second, the presence of bidirectional communication between the cerebellum and basal ganglia; third, the specific cortical areas that have monosynaptic and/or disynaptic connections to spinal motoneurons in non-human primates; and fourth, the areas in the cerebral cortex with the most direct influence on the sympathetic innervation of the kidney. These examples demonstrate the power of transneuronal tracing with rabies virus to identify the macroarchitecture of complex neural circuits.