Understanding Neural Networks: Identifying Monosynaptic Connections
Inventors: Edward Callaway, Ian Wickersham, and John Young
Potential Uses: Drug Discovery, CNS, Gene Expression
Transcomplemented Transsynaptic Tracing (A-C) Long-range viral spread from a single initially infected cell. (A) A huge cluster of green cells surrounds a single red/green deep-layer cortical neuron (dotted line) at 8 days postinfection. (B-C) Closeup of central cluster from (A). Scale bars: 200 mm.
We have identified a novel method for understanding neural networks by using a synaptic tracer that crosses only one synaptic step, unambiguously identifying cells directly presynaptic to the starting population so-called, the transcomplemented transsynaptic tracing method. To do this, we inject the cell population of interest with a deletion-mutant tracing virus that is missing one or more genes required for transsynaptic spread, and then complement this deletion by providing the missing viral genes in trans in the initially infected neurons only. With all the viral genes present in the starting cells, the virus can spread from them to cells in monosynaptic contact. Because those genes are not in the secondarily infected cells, however, the virus can't spread beyond them. Based on the rabies virus, this tracer is genetically targetable, allows high-level expression of any gene of interest in the synaptically coupled neurons, and is powerful enough to label neurons that connect to a single starting cell.
Patent Status: US Patent Application published as August 14, 2008
Publications: Neuron 53, 639-647 (March 2007)
License Terms: Exclusive, Partially Exclusive, Nonexclusive license negotiable
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