Action Potential

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.