Friday, December 13, 2013

Millisecond-timescale, genetically targeted optical control of neural activity.

Boyden ES, Zhang F, Bamberg E, Nagel G, Deisseroth K. Nat Neurosci. 2005 Sep;8(9):1263-8

Many people see optogenetics and Channelrhodopsin (ChR) as hot new tools to use for studying neuronal activity and connectivity, but (while I don't disagree about its hotness) it's actually not that new.  Some of the first papers published on channelrhodopsin come from 2002, in which both ChR1 and ChR2 were described.  While most people think of the Deisseroth lab when they think of ChR, these papers were actually published by two completely different groups (PMID: 12060707 and 12089443), although some of the authors later began collaborations with the Deisseroth lab.  What made Deissiroth famous, and rightly so, was this 2005 paper, in which he was the first to publish on using ChR in neurons (other groups worked in oocytes, HEK cells, etc) and recording their photoactivatable activity with whole-cell patch clamp.
In this paper, they harvested P0 rat hippocampal neurons, cultured them, and transfected them on day 7 with lentivirus in order to cause expression of ChR2-YFP.  Under voltage clamp, they found that they were able to induce inward currents with flashes of light (8-12mW/mm^2).  When they recorded in current clamp mode, they found that these currents were sufficient to cause action potentials at ~30Hz in some cases.  When they patched on to non-trasfected (non-fluorescent) cells, they were able to see excitatory and inhibitory postsynaptic potentials induced by the flashes of light that they could block with glutamatergic and gabaergic antagonists.
By showing that expression of light-gated in ion channels in neurons gives you precise temporal control of neuronal firing, this paper ushered in the age of optogenetics in neuroscience, and it is why many people think Deisseroth will eventually win the Nobel Prize.
Funny story: one of our own professors here at WSU SoM also did a lot of early work on ChR, except he thought the experiments in these papers were obvious, so he didn't do them.  He decided that since his lab works on the retina, he would use ChR in the eye - which didn't get anywhere near as much publicity when he published on using ChR to restore vision in mice suffering from photoreceptor degeration in early 2006.
-dh

No comments:

Post a Comment