Brainbow mice are out

2 11 2007

Jeff Lichtman‘s Brainbow mouse paper is out! Not that I really need to report that news, as it is, of course, on the cover of Nature. Jean Livet comes up with some really clever genetic strategies involving incompatible, overlapping Lox sites to generate random, combinatorial patterns of multiple fluorescent proteins inside the cell. Around 90 different shades can be discerned by spectral deconvolution.

Besides making pretty covers, why is this so cool?

Well, this technique provides a method for generating high resolution maps of the brain. With a single fluorescent tag, the processes of neighboring cells blur together and became impossible to trace unambiguously. With brainbow, many neighboring axons are clearly resolvable. This is the perfect genetic tool to use for a large-scale, all-out effort for the complete mapping of the circuitry of the mouse brain. It would be a tremendous challenge, but perhaps no more difficult than the human genome project. A large public consortium, or a Celera of the brain can really attack the connectivity problem now.

Of course, there still is the more difficult problem of showing the functional connectivity of the circuit map. Then again, this technique isn’t limited to swapping in static fluorescent tags. The insert cassette could be doped with a single FP functional indicator like G-CaMP2… Would this allow the combination of static circuit mapping with functional testing?


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5 responses

5 11 2007
christophe

On a related subject (optical monitoring of neuronal connectivity), there is also this paper by Rafa Yuste’s group in Nature Methods. It includes neuronal connectivity processing in parallel with calcium monitoring, although only in brain slices yet…

8 11 2007
Graham Ellis-Davies

It is not clear to me that any genetically encoded indicator works well in vivo yet?
Konnerth and collaborators had a nice paper in Nature Methods trying to do that, but you still can’t beat chemical Ca dyes!

Nat Methods. 2007 Feb;4(2):127-9.
Cell Calcium. 2007 Oct-Nov;42(4-5):351-61

8 11 2007
andrewhires

They are getting very very close to useable in vivo, but may never reach the S/N of dyes. But they have numerous other advantages… Probably Mazahir Hasan from Denk’s lab has done the most careful characterization of the currently available GECIs… He likes ours, d3cpv!

9 11 2007
Graham Ellis-Davies

I would like to add the paper by Svoboda’s lab to this discussion.

Pologruto TA, Yasuda R, Svoboda K Monitoring neural activity and [Ca2+] with genetically encoded Ca2+ indicators. J Neurosci. 2004 vol. 24 (43) pp. 9572-9.

This is the only paper that compares directly ca dyes with GECI. They use “old” CECI, but they show that the 3 they test do not work. I would encourage others maing GECI to do the same rigorous comparisons.

9 11 2007
Graham Ellis-Davies

I would like to add the paper by Svoboda’s lab to this discussion.

Pologruto TA, Yasuda R, Svoboda K Monitoring neural activity and [Ca2+] with genetically encoded Ca2+ indicators. J Neurosci. 2004 vol. 24 (43) pp. 9572-9.

This is the only paper that compares directly Ca dyes with GECI. They use “old” CECI, but they show that the 3 they test do not work. I would encourage others making GECI to do the same rigorous comparisons.

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