New Optogenetic Tool for Neural Inhibition

A fascinating paper from Gradinaru et al describes a genetically engineered mouse model of Parkinson's disease that expresses a photoreceptor in the neurons of a particular part of the brain - the subthalamic nucleus (STN). This area is widely thought to be the central target of the immensely therapeutic technique for Parkinson's known as deep brain stimulation. With this photoreceptor in place, the authors could direct laser light to that area of the brain and direactly affect neural activity - in particular, whether the behavioral symptoms of Parkinson's would disappear following absolutely precise targeting of the STN. The surprising result: Parkinson's symptoms were completely unaffected by this - instead, they were resolved only by targeting closely related structures.

This result is groundbreaking because it potentially refutes the most commonly held view of the STN's function. However, the photoreceptor used by Gradinaru et al was not 100% effective. Close inspection of their paper's figures reveals that they only inhibited the bursting activity usually found in STN - in contrast, the more tonic or baseline firing rate seemed unaffected. Observe:


Enter today's Nature paper by Chow et al, from Ed Boyden's group (btw, Ed runs a blog over at MIT's Tech Review). They demonstrate the near-total inhibition of mouse neurons (up to 100% reductions in firing rate with 200pA in vitro) using some new receptor types not previously explored for this purpose. Behold:


So, now we're left wondering whether this much more effective optogenetic technique might have yielded different results in the Gradinaru experiment. Here's hoping that Boyden's group plans to find out (and tell us!)...


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Optogenic toools provide a promising technique to study brain actions. The synapses in brain are complicated. A procedure on one synapse may be executed in the form of effect on other synapse. The original synapse or part of brain which was acted upon might remain unaffected. Targeting synapses in STN might not change the activities in STN but it might affect other areas as we got in Gradinaru experiment.