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      Monosynaptic restriction of transsynaptic tracing from single, genetically targeted neurons.

      Neuron
      Action Potentials, physiology, Animals, Avian Proteins, genetics, Biolistics, Excitatory Postsynaptic Potentials, Gene Deletion, Genetic Complementation Test, Green Fluorescent Proteins, Neural Pathways, cytology, Neurons, Organ Culture Techniques, Rabies Vaccines, pharmacokinetics, Rats, Receptors, Virus, Synaptic Transmission, Transfection, methods

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          Abstract

          There has never been a wholesale way of identifying neurons that are monosynaptically connected either to some other cell group or, especially, to a single cell. The best available tools, transsynaptic tracers, are unable to distinguish weak direct connections from strong indirect ones. Furthermore, no tracer has proven potent enough to label any connected neurons whatsoever when starting from a single cell. Here we present a transsynaptic tracer that crosses only one synaptic step, unambiguously identifying cells directly presynaptic to the starting population. Based on rabies virus, it is genetically targetable, allows high-level expression of any gene of interest in the synaptically coupled neurons, and robustly labels connections made to single cells. This technology should enable a far more detailed understanding of neural connectivity than has previously been possible.

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