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Optogenetics Comes to the Rat Brain

30 December 2011. Optogenetics is no longer just for the mouse. A team of researchers, led by Karl Deisseroth of Stanford University in Stanford, California and Patricia Janak, of the University of California San Francisco, reports the creation of several transgenic rat lines that allow for the optical control of specific catecholamine neurons.

Optogenetics has proved to be a revolutionary technique: By pairing genetics (insertion of a gene for light-activated proteins, or opsins, into specific cells) with optics (use of light to stimulate those cells), researchers can control defined cell populations in awake behaving mice with high temporal precision—on the scale of milliseconds. Deisseroth’s group has already used this tool to show that parvalbumin neurons are critical for gamma oscillations (SRF related news story) and that altering the excitatory/inhibitory balance of the mouse brain produces behavioral abnormalities reminiscent of schizophrenia (SRF related news story). Until now, however, this technique has been used exclusively in mice. In the current study, first author Ilana Witten and colleagues have created a series of transgenic rat lines expressing the DNA recombination enzyme Cre recombinase in specific cell types, enabling future optogenetics experiments in the rat, the rodent model of choice in many areas of neuroscience research.

Putting one of their novel transgeneic rat lines to work, Witten and colleagues used optogenetics to address an old question: does stimulation of dopamine neurons in the ventral tegmental area, a region long implicated in reward processing, underlie intracranial self-stimulation? Previous attempts to link dopamine neuron activation with self-stimulation behavior have proved difficult due to the GABAergic and glutamatergic interneurons that are also present and therefore activated during electrical stimulation of the VTA ( Fields et al., 2007). In the current study, however, optogenetics allowed the researchers to activate only dopamine neurons. Following injection of a Cre-dependent opsin virus into the VTA of transgenic rats expressing Cre in dopamine neurons, administration of blue light pulses resulted in vigourous self-stimulation behavior, indicating that activation of dopamine neurons is sufficient to produce such behavior.—Allison A. Curley.

Witten IB, Steinberg EE, Lee SY, Davidson TJ, Zalocusky KA, Brodsky M, Yizhar O, Cho SL, Gong S, Ramakrishnan C, Stuber GD, Tye KM, Janak PH, Deisseroth K. Recombinase-Driver Rat Lines: Tools, Techniques, and Optogenetic Application to Dopamine-Mediated Reinforcement. Neuron. 2011; 72: 721-733. Abstract

Comments on News and Primary Papers
Comment by:  Bryan Roth, SRF Advisor
Submitted 16 December 2011 Posted 21 December 2011
  I recommend the Primary Papers

This will be a valuable resource for those who use rats...  Read more

View all comments by Bryan Roth
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I recommend the Primary Papers

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