Monday, November 14, 2011

Why cheap techniques are not always good

Yesterday there was a whole alley of posters about optogenetics here at the SfN meeting. Of course this technique is very hot, easy and cheap to use. So, it was to be expected that a lot of labs would jump on the bandwagon. Unfortunately, most research was not very interesting. Or rather, very not interesting: "We used optogenetics to look at attention", "We made a new virus that performs slightly worse than what is available", "We introduced optogenetics into the common hedgehog, and guess what; it does what it's supposed to do!", "We used optogenetics to...". You get what I mean....

Fortunately, among all this nonsense there were a few gems. One poster finally solved convincingly the debate how many cerebellar molecular layer interneurons provide input to one Purkinje cell. This question is more complicated than it seems since molecular layer interneurons are electrotonically coupled. When coupling is strong you can have indirect effects of multiple cells through other interneurons. The lab of G.J. Augustine from Duke University used ChR2 expression in interneurons to map the spatial extent of inputs from molecular layer interneurons to one patched Purkinje cell. First they mapped the spatial extent of one interneuron by patching it and scanning the slice looking for direct activation. The spatial extent of one neuron turned out to be ~5500um2. Then, by mapping the input to one Purkinje cell they estimated that five to six interneurons are involved in providing inhibitory input to one Purkinje cell. After blocking gap junctions this number reduced to ~2 interneurons. Interestingly, this effect completely disappeared when coronal slices were used. This confirms that interneurons are coupled in the sagittal plane and interneurons can influence distant Purkinje cells in the same zone.

An other poster was about the difference between somatostatin and parvalbumin positive interneurons in the visual cortex. M. Sur's lab from MIT used celltype specific virus-driven expression of ChR2 to probe the functional impact of interneurons in vivo. Tuning curves for Pyramidal cells were determined by providing moving gratings and imaging the pyramidal cell's responses using calcium imaging. When PV neurons were activated, the pyramidal cell's response showed a scaling of the response. In contrast, SOM interneurons provided a subtractive operation. Clearly the two neuron classes have different functional implications. Since PV interneurons project mainly to the soma of cells and SOM interneurons mainly to the dendrites, it would be interesting to see whether this effect would hold for other brain areas as well where inhibitory input is differentially provided to somata and dendrites.

Clearly, optogenetics is a powerful tool when used correctly. It's always been the same: techniques should never be leading in research, questions should.

No comments: