Monosynaptic restriction of transsynaptic tracing from single, genetically targeted neurons.
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.
Wickersham
Ian R
IR
Systems Neurobiology, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Lyon
David C
DC
Barnard
Richard J O
RJ
Mori
Takuma
T
Finke
Stefan
S
Conzelmann
Karl-Klaus
KK
Young
John A T
JA
Callaway
Edward M
EM
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D030161:Avian Proteins / Q000235:genetics; D019470:Biolistics; D019706:Excitatory Postsynaptic Potentials; D017353:Gene Deletion; D005816:Genetic Complementation Test; D049452:Green Fluorescent Proteins / Q000235:genetics; D009434:Neural Pathways / Q000166:cytology*; D009474:Neurons / Q000166:cytology* / Q000502:physiology; D009924:Organ Culture Techniques; D011819:Rabies Vaccines / Q000235:genetics* / Q000493:pharmacokinetics; D051381:Rats; D011991:Receptors, Virus / Q000235:genetics; D009435:Synaptic Transmission / Q000235:genetics*; D014162:Transfection / Q000379:methods
D030161:Avian Proteins; D011819:Rabies Vaccines; D011991:Receptors, Virus; C088745:Tva receptor; D049452:Green Fluorescent Proteins