First Guest-Blog: Questioning OptogeneticsPosted on November 11, 2011
Yesterday I marked a few posters about optogenetics in my itinerary. When I arrived at the alley where they were located I was shocked to see a big mass of people pushing and fighting to see all posters there. One couldn’t fail to notice that optogenetics is hot!
Of course the technique is inexpensive and yes you can do awesome research with it. The problem is, most people don’t. There were posters about the development of new vectors (“We made a new virus that performs slightly worse than what is available”), new probes, outrageous applications and a whole lot of other things people will forget about in a year or so (“We introduced optogenetics into the common hedgehog, and guess what; it does what it’s supposed to do!”). Fortunately, Amidst all this, there were a few posters that were gems. I’ll highlight two of them:
The lab of G.J. Augustine from Duke University showed that Purkinje cells receive input from just 1-2 interneurons directly and from 3-4 interneurons indirectly via electrotonic coupling. They did this by first measuring the extent of the dendritic tree of one interneuron in the slice by patching it and stimulating the slice at several points creating a ‘map’ of the neuron. By now comparing the spatial extent of one interneuron to the area from which one Purkinje cell can be inhibited, you can estimate the number of interneurons involved in this inhibition. Furthermore, by blocking the gap junctions they estimated that ~2 interneurons provide direct inhibition and 3-4 provide inhibition via coupling. Maybe the most interesting fact was that this indirect inhibition was completely gone in coronal slices, confirming that interneurons provide inhibition within one cerebellar zone.
Another poster from the lab of M. Sur from MIT showed the difference between Parvalbumin (PV) and Somatostatin (SOM) neurons. Interneurons don’t just provide inhibition and ‘block’ spikes. They provide arithmetic operations. Apparently the PV neurons provide a divisive operation (scaling) while SOM neurons provide a subtractive operation. They found this by looking at pyramidal cell responses during the acquisition of a tuning curve. When PV neurons were stimulated during the acquisition, the pyramidal cell response amplitude was scaled down. In contrast, when SOM neurons were stimulated the tuning curve shifted downward in its entirety. Clearly, the two interneuron classes have a completely different role in shaping the pyramidal cell response.
As you can see, when the scientific question is sound, optogenetics can be a powerful tool. It’s always been the same: techniques should never be leading in research, questions should.
written by: mouseguy