Pseudorabies virus as a transneuronal tract tracing tool: specificity and applications to the sympathetic nervous system.

Because of technical shortcomings, neuroanatomical tract tracing methods have been limited in their ability to examine functional pathways. This has been particularly true of the study of the sympathetic nervous system. Peripheral targets of the sympathetic nervous system are innervated by sympathetic ganglion cells which are located in various, discreet ganglia, primarily in the abdomen and thoracic cavity. Each ganglion contains neurons innervating multiple targets. In turn, each ganglion is innervated by preganglionic motor neurons located in the thoracic and lumbar spinal cord. Preganglionic neurons are innervated by neurons from the brainstem and hypothalamus, as well as probably by spinal interneurons. At each of these sites, the ganglia, the preganglionic nuclei of the spinal cord, and the brainstem and hypothalamus, functionally different neurons are intermingled. Therefore, placement of a traditional retrograde marker (i.e. HRP) in any of those sites would generate retrogradely labeled neurons that represent multiple functional pathways, making the study of one functional pathway impossible. A transneuronal retrograde tracer could obviate this problem by passing the original tracer from the first neuron labeled transsynaptically to neurons which synapse on to it. After injection of the transneuronal tracer into a peripheral target, the tracer would be transported, first to the ganglion cell, then to the preganglionic neurons that innervate the ganglion cell, and then to the neurons in the brain that innervate the preganglionic neurons. All the neurons labeled would belong to one functional pathway, specifically involved in control of that target which was injected. There have been attempts to develop such tracers. WGA-HRP, tetanus toxin, and the tetanus toxin C-fragment have been used with limited success (1,2,3,4,5).(ABSTRACT TRUNCATED AT 250 WORDS)