( t the chain of directly connecting neur...)Deconstructing brain wiring, one neuron at a time

Viruses that naturally spread between neurons have previously been used to outline the flow of nerve cell communication, but they have two drawbacks. First, once inside the brain, they keep spreading from cell to cell without stopping. Second, they cross different synapses ?the specialized junctions between nerve cells - at different rates, crossing bigger, stronger synapses faster than smaller, weaker ones. Together these attributes make these viruses unable to determine exactly which cells are connected to which. The team of Salk researchers sought to create a modified virus whose spread could be limited to a single synaptic connection.

"The core idea is to use a virus that is missing a gene required for spreading across synapses but to provide the missing gene by some other means within the initially infected cells," says Ian Wickersham, Ph.D., postdoctoral researcher and lead author on the project.

With the critical gene deleted from its genome, the virus is marooned inside a cell, unable to spread beyond it. However, supplying the missing gene in that same cell allows the virus to spread to cells that are directly connected to it. Since these neighboring cells lack the gene supplied in the first cell, the virus is stuck. Only the cells connected directly to the original cell are labeled.

The team's second challenge was to find a way of targeting the viral infection specifically to particular cells, so that the virus could be used to map the connections of cell types of interest or even of single cells. The solution came from a conversation between Callaway and John Young, Ph.D., a Professor in the Infectious Disease Laboratory, and co-author of the study. When Callaway described the problem, Young immediately suggested the answer, which is based on an avian viral receptor that Young discovered as a postdoctoral fellow at UCSF. The protein that ord
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Source:Salk Institute