A multi-faceted toolkit for all scientists to use
Called "Cre driver lines," Dr. Huang's approach makes use of a well-established and widely used technique called Cre-Lox recombination to create the equivalent of genetic handles in specific types of cells within the cerebral cortex. Different strains of mice have been developed, each to express a particular gene or genes that enable microscopists to home in on particular subtypes of GABA neurons. The key, Huang explains "is that the 'driver' in each case is a gene that we know something about. We know its expression correlates with a subset of GABA neurons. We use that gene as a kind of entry point to express various kinds of markers."
The current paper describes 20 mouse lines that have been engineered in various ways. These can be used to activate molecular "reporters" that label different GABA cell types, or to make the targeted cells responsive to beams of colored laser light a technique called optogenetics. They also enable researchers to follow axonal paths that connect particular GABA cells with other cells by incorporating deactivated retroviruses. "Optogenetics and retroviral labeling are wonderful techniques, but they are not, by themselves, cell-type specific. We've built a system that integrates all of these technologies, which can now be mobilized with exquisite specificity," Huang says.
The net result is a toolkit which will grow to include more mouse lines -- for the use of experimentalists in labs everywhere, and which enables comprehensive and systematic exploration of inhibitory GABA neurons. Perhaps most exiting to Huang is the opportunity to view the manner in which inhibition functions in a living brain.
"The functional circuit, even though it is s
|Contact: Peter Tarr|
Cold Spring Harbor Laboratory