A Cre-Dependent, Anterograde Transsynaptic Viral Tracer for Mapping Output Pathways of Genetically Marked Neurons
Neurotropic viruses that conditionally infect or replicate in molecularly defined neuronal subpopulations, and then spread trans-synaptically, are powerful tools for mapping neural pathways. Genetically targetable retrograde trans-synaptic tracer viruses are available to map the inputs to specific neuronal subpopulations, but an analogous tool for mapping synaptic outputs is not yet available. Here we describe a Cre recombinase-dependent, anterograde trans-neuronal tracer, based on the H129 strain of herpes simplex virus (HSV). Application of this virus to transgenic or knock-in mice expressing Cre in peripheral neurons of the olfactory epithelium or the retina reveals widespread, polysynaptic labeling of higher-order neurons in the olfactory and visual systems, respectively. Polysynaptic pathways were also labeled from cerebellar Purkinje cells. In each system, the pattern of labeling was consistent with classical circuit-tracing studies, restricted to neurons and anterograde-specific. These data provide proof-of-principle for a conditional, non-diluting anterograde trans-synaptic tracer for mapping synaptic outputs from genetically marked neuronal subpopulations.
© 2011 Elsevier Inc. Under an Elsevier user license. Accepted: December 1, 2011. Published: December 21, 2011. We thank Dr. L. Enquist for the H129 strain of HSV1, advice, and encouragement throughout this project and for feedback on the manuscript, Dr. Jerry Weir for plasmid pGAL10, Dr. Joseph Gogos for OMP-Cre mice, Dr. Markus Meister for help with visual system circuitry, Drs. A. Basbaum and E. Callaway for helpful comments on the manuscript, G. Mosconi and H. Oates-Barker for laboratory management, and G. Mancuso for administrative assistance. This work was supported by NIH grant 1RO1MH070053. D.J.A. is an Investigator of the Howard Hughes Medical Institute. Accession Numbers The cmHTK sequence and plasmid have been deposited at Addgene (plasmid 34563; http://www.addgene.org/34563/).
Accepted Version - nihms347084.pdf