Here is a very cool experiment from Ed Boyden’s lab at MIT: they have used a fungus (yes, you read that right – a fungus) to turn off neurons using a proton pump that is turned on by blue-green light. Sure, the neurons were in a culture. Sure, they weren’t human neurons. But this is seriously interesting because, together with the rapidly advancing understanding of brain cells important in chronic pain, we might be on the path to turning off pain. I bet this is the general theme of the cover letter Ed Boyden wrote to Nature and I reckon it is a fair, speculative, but not outrageous, proposal. It is certainly fundamental research and probably decades ‘pre-clinical’, but just let your pragmatic realism go for a moment and imagine…..let’s say we learn how to identify which brain cells are mediating chronic pain in a particular individual, then we use some mushroom-derived proton pump to turn them off. That is an exciting prospect. Then again, are we kidding ourselves to think it will, one day, be this simple. I hope not, but I can’t ignore this whispering in my mind – ‘we are fearfully and wonderfully complex’. Perhaps we will, perhaps we won’t – regardless, i reckon Ed Boyden and his team should be congratulated. In fact, I have reason to believe – our invitation to Ed to write this having just been turned down – that he and his family have even better reasons to be congratulated! Congatulations on both fronts I say! Here is the link to the paper:
Brian Y. Chow(1,2,3), Xue Han(1,2,3), Allison S. Dobry(1,2), Xiaofeng Qian(1,2), Amy S. Chuong(1,2), Mingjie Li(1,2), Michael A. Henninger(1,2), Gabriel M. Belfort(2), Yingxi Lin(2), Patrick E. Monahan(1,2) & Edward S. Boyden(1,2)
1. The MIT Media Laboratory, Synthetic Neurobiology Group, and Department of Biological Engineering,
2. Department of Brain and Cognitive Sciences and MIT McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
3. These authors contributed equally to this work.
The ability to silence the activity of genetically specified neurons in a temporally precise fashion would provide the opportunity to investigate the causal role of specific cell classes in neural computations, behaviours and pathologies. Here we show that members of the class of light-driven outward proton pumps can mediate powerful, safe, multiple-colour silencing of neural activity. The gene archaerhodopsin-3 (Arch)1 from Halorubrum sodomense enables near-100% silencing of neurons in the awake brain when virally expressed in the mouse cortex and illuminated with yellow light. …….. To highlight how proton pump ecological and genomic diversity may support new innovation, we show that the blue–green light-drivable proton pump from the fungus Leptosphaeria maculans 4 (Mac) can, when expressed in neurons, enable neural silencing by blue light, thus enabling alongside other developed reagents the potential for independent silencing of two neural populations by blue versus red light. Light-driven proton pumps thus represent a high-performance and extremely versatile class of ‘optogenetic’ voltage and ion modulator, which will broadly enable new neuroscientific, biological, neurological and psychiatric investigations.
Chow BY, Han X, Dobry AS, Qian X, Chuong AS, Li M, Henninger MA, Belfort GM, Lin Y, Monahan PE, & Boyden ES (2010). High-performance genetically targetable optical neural silencing by light-driven proton pumps. Nature, 463 (7277), 98-102 PMID: 20054397