Exploring brain circuitry with neurotropic viruses: New horizons in neuroanatomy

There have been substantial advances in methods for defining connections am ong neurons over the past quarter century, However, most tracers have been limited in their ability to define populations of functionally related neur ons that contribute to a multisynaptic circuit because they are not transpo rted across synapses, As a result, the large body of literature that has em ployed these tracers has established regional associations between regions that must be further explored with electron microscopy and electrophysiolog ical methods to define the synaptic relations among constituent neurons. Re cently, neurotropic alpha herpesviruses have been used to visualize ensembl es of neurons that contribute to polysynaptic networks, These pathogens inv ade permissive cells, replicate, and pass transynaptically to infect other neurons. In effect, the viruses become self-amplifying tracers whose natura l tropism and invasiveness define populations of functionally related neuro ns, The recent increase in the use of this experimental approach has emerge d from advances in our understanding of the life cycle of these viruses and the resulting evidence in support of specific transynaptic passage of prog eny virus rather than infection by lytic release into the extracellular spa ce, This article reviews the advances that have made this a viable experime ntal approach and considers ways in which this method has been creatively u sed to illuminate aspects of nervous system circuit organization that could not be defined with conventional tracers, Anat, Rec, (NewAnat,) 253:175-18 5 1998, (C) 1998 Wiley-Liss, Inc.