DISTRIBUTION OF VESICULAR STOMATITIS-VIRUS PROTEINS IN THE BRAINS OF BALB C MICE FOLLOWING INTRANASAL INOCULATION - AN IMMUNOHISTOCHEMICAL ANALYSIS/

Earlier studies have shown that intranasal instillation of vesicular s tomatitis virus (VSV), a negative-sense RNA virus, in mice and rats ca n result in infection of the brain, hind-limb paralysis and death. Usi ng an antiserum directed against VSV proteins, we sought to determine the potential neuronal and non-neuronal pathways VSV utilize, for cent ral nervous system dissemination in BALB/c mice. Within 12 h following intranasal inoculation of VSV, VSV antigen could be detected in the o lfactory nerve layer of the ipsilateral olfactory bulb. Within 3-4 day s post-inoculation (p.i.), VSV had disseminated into the glomeruli of the olfactory bulb as well as the anterior olfactory nuclei that were ipsilateral to the VSV instillation. Within the glomeruli, VSV antigen was more prevalent in the granule cells than in the mitral cells. Cor respondingly, the lateral olfactory tract, where axons of mitral cells course, remained VSV negative throughout 7 days p.i. By 7 days p.i., viral proteins were detected in several additional regions extending t o the brainstem. These included regions involved in theta-rhythm gener ation during exploration and REM sleep, i.e. the septal nuclei, the su pramammilary body, and the hippocampal formation, as well as the amygd aloid complex and brainstem neuromodulatory centers, such as the dorsa l raphe and locus coeruleus. Structures abutting the ventricular surfa ces, such as the dorsal cochlear nucleus, were also labeled. Tracts im munoreactive to VSV included the dorsal tegmental tract, fascia retrof lexus, Probst tract, and mesencephalic tract of the trigeminal motor n erve. Besides the lateral olfactory tract, tracts that remained VSV ne gative included the anterior commissure, the corpus callosum and the m ammillary peduncle. The pattern of VSV immunoreactivity supports the i dea that following infection of the olfactory bulb glomeruli, VSV spre ads via both ventricular surfaces and retrograde transport within axon s of neuromodulatory transmitter systems innervating the olfactory bul b. Conversely, regions exhibiting low levels of VSV antigen are not li kely to be involved in VSV dissemination. In particular, the paucity o f VSV antigen in some of the terminal fields of neuromodulatory system s indicate that anterograde transport is more selective than retrograd e transport. Surprisingly, the principal neurons of the olfactory glom eruli, thalamus, cerebral cortex and the hippocampus, all of which use L-glutamate as the excitatory neurotransmitter, are much less involve d in viral dissemination.