Axel versus Miesenbock: what in a name?
The fluorescence of GFP is pH sensitive, and so mutants of GFP have been made to counteract this problem. In 1998 Gero Miesenbock published a paper as a postdoc in Jim Rothman's lab in Nature using the weakness of GFP to his advantage. He tagged GFP with a synaptic vesicle protein so that when the vesicle fused with the plasma membrane, the exocytotic event was signalled by light. GFP was, in effect, a "flare" for synaptic activity (they were dubbed "synapto-pHluorins"). Miesenbock left Jim Rothman's lab, but stayed at Sloan to published the first creative application of this new probe in August 2002. I heard Gero give a presentation of this work at the McKnight annual conference in June of that year, and was amazed by the presentation. He had built his own video-rate 2-photon microscope so he could image synaptic activity in vivo using his synapto-pHluorins. His lab targeted the probe to the Drosophila antenal lobe, and depending on the type of odor (banana, cherry, apple), they found different populations and combinations of glomeruli "lit up"; so they were able to see dynamic odor representation for the first time, "in elements of the olfactory that had previously been inaccessable to direct optical analysis, in any species".
In October 2002 Richard Axel submitted a paper to Cell doing the similar studies, but using a GFP-based Ca probe (caled G-CaMP) as the indicator of synaptic activity. He makes only passing mention of Miesenbock's earlier paper, saying, "Recently, imaging studies with synapto-pHluorin, a fluorescent indicator of pH change, have revealed dense patterns of glomerular activity in the fly antennal lobe (Ng et al., 2002). This fluorescent indicator has been ex pressed in defined neurons and affords spatial resolution but has limited sensitivity due to low signal-to-noise ratio. As a consequence, analysis requires non-physio- concentrations that may result in spatial representations not naturally encountered by the fly brain." What Axel fails to mention is that his GFP-based Ca indicator is very slow and because it requires 4 calciums to give a signal, will heavily buffer Ca in an uncontrolled way, undoubtedly dramatically purterbing synaptic actvity. (As a further technical aside, since Axel used galvonometers, the imaging reported would have been slow, even if his probe was fast!). This comment is burried in the results section, giving the impression it is not really important, whereas in effect Axel had merely followed on from the pioneering work of the Miesenbock lab (Axel was in fact on Sloan-Kettering's scientific advisory board at that time). Don't get me wrong, both papers are great, but shouldn't a big shot give credit to a young scientist? It is not as if Axel he needed just one more Cell paper to get the Nobel (to his credit, Axel does at least mention Miesenbock's paper in his Nobel Address in 2004).
However, to date, Axel's paper has been cited about 120 times and Misenbock's 70.
What's in name? Apparently quite a lot.
Ng M, Roorda RD, Lima SQ, Zemelman BV, Morcillo P, Miesenbock G. Transmission of olfactory information between three populations of neurons in the antennal lobe of the fly. Neuron (2002) 36:463-474.
Wang JW, Wong AM, Flores J, Vosshall LB, Axel R Two-Photon Calcium Imaging Reveals an Odor-Evoked Map of Activity in the Fly Brain. Cell (2003) 112: 271-282.
The fluorescence of GFP is pH sensitive, and so mutants of GFP have been made to counteract this problem. In 1998 Gero Miesenbock published a paper as a postdoc in Jim Rothman's lab in Nature using the weakness of GFP to his advantage. He tagged GFP with a synaptic vesicle protein so that when the vesicle fused with the plasma membrane, the exocytotic event was signalled by light. GFP was, in effect, a "flare" for synaptic activity (they were dubbed "synapto-pHluorins"). Miesenbock left Jim Rothman's lab, but stayed at Sloan to published the first creative application of this new probe in August 2002. I heard Gero give a presentation of this work at the McKnight annual conference in June of that year, and was amazed by the presentation. He had built his own video-rate 2-photon microscope so he could image synaptic activity in vivo using his synapto-pHluorins. His lab targeted the probe to the Drosophila antenal lobe, and depending on the type of odor (banana, cherry, apple), they found different populations and combinations of glomeruli "lit up"; so they were able to see dynamic odor representation for the first time, "in elements of the olfactory that had previously been inaccessable to direct optical analysis, in any species".
In October 2002 Richard Axel submitted a paper to Cell doing the similar studies, but using a GFP-based Ca probe (caled G-CaMP) as the indicator of synaptic activity. He makes only passing mention of Miesenbock's earlier paper, saying, "Recently, imaging studies with synapto-pHluorin, a fluorescent indicator of pH change, have revealed dense patterns of glomerular activity in the fly antennal lobe (Ng et al., 2002). This fluorescent indicator has been ex pressed in defined neurons and affords spatial resolution but has limited sensitivity due to low signal-to-noise ratio. As a consequence, analysis requires non-physio- concentrations that may result in spatial representations not naturally encountered by the fly brain." What Axel fails to mention is that his GFP-based Ca indicator is very slow and because it requires 4 calciums to give a signal, will heavily buffer Ca in an uncontrolled way, undoubtedly dramatically purterbing synaptic actvity. (As a further technical aside, since Axel used galvonometers, the imaging reported would have been slow, even if his probe was fast!). This comment is burried in the results section, giving the impression it is not really important, whereas in effect Axel had merely followed on from the pioneering work of the Miesenbock lab (Axel was in fact on Sloan-Kettering's scientific advisory board at that time). Don't get me wrong, both papers are great, but shouldn't a big shot give credit to a young scientist? It is not as if Axel he needed just one more Cell paper to get the Nobel (to his credit, Axel does at least mention Miesenbock's paper in his Nobel Address in 2004).
However, to date, Axel's paper has been cited about 120 times and Misenbock's 70.
What's in name? Apparently quite a lot.
Ng M, Roorda RD, Lima SQ, Zemelman BV, Morcillo P, Miesenbock G. Transmission of olfactory information between three populations of neurons in the antennal lobe of the fly. Neuron (2002) 36:463-474.
Wang JW, Wong AM, Flores J, Vosshall LB, Axel R Two-Photon Calcium Imaging Reveals an Odor-Evoked Map of Activity in the Fly Brain. Cell (2003) 112: 271-282.
posted by graham at 10:19 AM
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