Action Potential

Is it all about timing?

Just a few weeks can separate a splash from a quiet ripple. On 5 April, Neuron and Nature both published articles reporting genetically targeted silencing of mammalian neurons. In Neuron, Lerchner et al. detailed drug-induced hyperpolarization of neurons expressing a C. elegans chloride channel within hours of treatment. In Nature, Zhang et al. reported light-induced hyperpolarization of neurons expressing an archaea opsin within milliseconds of illumination. The media took note of Zhang’s article, but not Lerchner’s.

To be fair, the two articles are quite different in scope. Zhang et al. reported not just inducible neuron silencing, but a neuron on/off switch. In the same neuron, the authors induced firing with a blue light-activated cation channel and inhibited endogenous firing with a yellow-light induced chloride pump. They turned behaviors on and off with blue and yellow light, respectively, in C. elegans expressing both the cation channel and the chloride pump. The ability to control neuron function is nothing short of stunning and will undoubtedly impact both bench and bedside.

Although their scope was much smaller, Lerchner et al. approached neuronal silencing cleverly. Ivermectin is a chloride channel agonist in C. elegans, but not mammals, making it a potent antiparasitic agent that literally puts worms to sleep, sparing mammalian hosts. The authors silenced mammalian neurons expressing the C. elegans ivermectin-gated chloride channel and suppressed behavior with systemic treatment of ivermectin.

Systemic drug treatment is virtually guaranteed to take longer than illumination to achieve inhibition. And an off switch alone can’t compare to the deluxe on/off model. But I can’t help wondering if I’d be more excited about Lerchner’s article if it came out a few weeks earlier.

There is one interesting postscript to Zhang’s amazing achievement. Han and Boyden reported an identical yellow-light induced chloride pump earlier in the month in PLoS ONE. They examined the properties of blue and yellow light-induced excitation and inhibition in cultured hippocampal neurons. Although Han and Boyden don’t show any in vivo data, their study technically preceded Zhang et al. So, in the grand scheme of things, who will be credited with the discovery? Maybe timing isn’t everything.


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    Chris Surridge said:

    As with all scientific discoveries we will have to wait and see whose approach proves to be the more useful in the long term.

    Talking of timing the Nature news article accompanying the Zhang et al. paper (Proteins make light work of nerve control) has an interesting sentence: “Boyden,…., hurried through a report last month on the activity of NpHR”. Looking at the submissions dates Boyden submitted his paper to PLoS ONE on the 11th December 2006, Zhang et al. to Nature on 23rd December 2006. Acceptance dates were similarly spaced (Boyden, 24 February; Zhang, 14th March). I guess that means that Nature thinks that they ‘hurried’ their paper too.

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    Anonymous said:

    Why on earth are you calling this “Zhang’s amazing achievement”? Han and Boyden submitted their paper first, and published it first. And the media took notice — searching Google News reveals equal numbers of news reports describing each person’s work.

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    Debra Speert said:

    While you raise an interesting point, Anonymous, my aim was to compare two articles published on the same day (Zhang et al. and Lerchner et al.) that reported inducible suppression of neuronal activity in vivo.

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    Anonymous said:

    Han and Boyden may have published first, but the research was started while Boyden was in Deisseroth’s lab.

    Many researchers do not feel comfortable with the way Boyden “scooped” his ex-PI and claimed the discovery as his own, only months after starting his own lab at MIT.

    What do you think?

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    Debra Speert said:

    Thanks to everyone for their comments. In case you missed Annette’s earlier post, I’d just like to remind everyone that we strongly encourage those posting comments to use their full names.

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    Anonymous said:

    I heard from several people in the know, that Boyden started the work long before he met Deisseroth.

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    Debra Speert said:

    Thanks again for participating in this lively discussion. Although we encourage you to continue commenting, we will no longer publish anonymous comments on this thread. For further comments, please include your full name.