A Cre-dependent, anterograde transsynaptic viral tracer for mapping output pathways of genetically marked neurons

Neuron. 2011 Dec 22;72(6):938-50. doi: 10.1016/j.neuron.2011.12.002.

Abstract

Neurotropic viruses that conditionally infect or replicate in molecularly defined neuronal subpopulations, and then spread transsynaptically, are powerful tools for mapping neural pathways. Genetically targetable retrograde transsynaptic 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 transneuronal tracer, based on the H129 strain of herpes simplex virus (HSV). Application of this virus to transgenic or knockin 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, nondiluting anterograde transsynaptic tracer for mapping synaptic outputs from genetically marked neuronal subpopulations.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Axonal Transport / genetics
  • Chlorocebus aethiops
  • Gene Knock-In Techniques
  • Gene Targeting / methods*
  • Genetic Markers / genetics
  • Herpesvirus 1, Human / enzymology*
  • Herpesvirus 1, Human / genetics*
  • Humans
  • Integrases / genetics*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neural Pathways / enzymology
  • Neural Pathways / virology
  • Neurons / enzymology*
  • Neurons / virology*
  • Recombination, Genetic*
  • Synaptic Transmission / genetics*
  • Vero Cells

Substances

  • Genetic Markers
  • Cre recombinase
  • Integrases