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Yizhar O, Fenno LE, Prigge M, Schneider F, Davidson TJ, O'Shea DJ, Sohal VS, Goshen I, Finkelstein J, Paz JT, Stehfest K, Fudim R, Ramakrishnan C, Huguenard JR, Hegemann P, Deisseroth K. Neocortical excitation/inhibition balance in information processing and social dysfunction. Nature . 2011 Sep 8 ; 477(7363):171-8. PubMed Abstract

Comments on Paper and Primary News
Comment by:  Patricio O'Donnell, SRF Advisor
Submitted 2 August 2011 Posted 2 August 2011

A question that comes to mind to most when reading an article such as the one Yizhar et al. published online July 27 in Nature is: is this a big step forward or a flashy way to show what we already know? The answer is: both. It has to be.

Optogenetic tools to address neurobiological questions in a well-controlled manner, with selective activation or inactivation of specific brain areas and even cell types, pioneered by Karl Deisseroth’s group, have been around for some time. Deisseroth deserves recognition for developing such a clever tool, but even stronger recognition for proactively sharing these tools with anyone who requests them.

So far, optogenetic tools have been mostly used to address questions for which there were extensive previous studies, albeit with less conclusive techniques. Naturally, some would see that as just a replication of existing knowledge. However, an important first step for a novel tool like this one is to establish credibility, and what better approach than tackling questions for which we know the answer? For example, a couple of papers...  Read more

View all comments by Patricio O'Donnell

Comment by:  Cynthia Shannon Weickert, SRF AdvisorDuncan SinclairVibeke Catts
Submitted 29 August 2011 Posted 29 August 2011

Optogenetics Stimulates Our Thinking About Cortical Pathology in Schizophrenia
We recently reviewed this paper in the weekly Journal Club at the Schizophrenia Research Laboratory in Sydney, Australia. Here are some brief thoughts from our discussion:

First, we were very impressed with the development of the novel stable step function opsin (SSFO) and the anatomical and temporal precision with which it can be used in the mouse. Particularly powerful is the ability to induce cortical excitation in a time frame long enough to impact behavior without the confound of developmental compensatory change, as may occur in genetically engineered mice. The paper did raise a few questions in our minds about how to best relate this to findings in schizophrenia, especially in light of the ongoing debates as to: 1) whether the cortex is actually overactive or underactive (hyperactivity versus hypoactivity by fMRI); 2) whether the cortex shows increased γ band synchrony (at baseline) or decreased γ band synchrony (induced); and 3) whether there is more or less GABA...  Read more

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