What's Hot in PD? Shining a Light on Parkinson’s Disease: Optogenetics Has a Bright Future in Research

Francis Crick, one of the most famous scientists of our generation, described a double helix structure that is now known to characterize human DNA (this discovery was published in 1953 along with his colleague James Watson). Later, in the 1970s, Crick discussed a wish-list for future discoveries, including the use of light to control human cells. Light science and light therapy have since been considered both "crazy and far-fetched"; however, recent discoveries in the early 21st century have dramatically changed this point of view. Thanks to some very clever scientists, a new field called optogenetics was born.

What is optogenetics? The "opto-" refers to placing light onto the brain to activate channels and/or enzymes that will ultimately change brain cell firing. The technique is specific, and has the potential to add or delete firing patterns from the brain's native cells. Additionally, brain cell firing can be manipulated at precise millisecond intervals. The fiber-optic light source can be mounted on the skull, or placed deep within the brain. The genetics part of optogenetics utilizes simple virus carrier systems to deliver genes to the brain. The most important of these genetic deliveries has been opsin. Opsin is one of the structures potentially turned on by the light. The most important known opsin used for this technology is Channelrhodopsin-2, and it was derived by scientists from algae-based systems. By shining light onto the inserted genetic alteration (opsin), scientists can probe the brain's inner conversations (firing of cells). The technique has allowed investigators to move past the classical genetic manipulation, which has much less specificity.

Last week Kravitz and colleagues (from the pioneering optogenetics group at Stanford) published an important paper in Nature. They were able to demonstrate that optogenetics could either worsen or alternatively improve an animal model of Parkinsonism. The investigators performed a simple experiment where they manipulated the well-established basal ganglia direct and indirect pathways, which are the best known suspects implicated in the genesis of Parkinson's disease. The authors reported "optogenetic control of direct- and indirect-pathway medium spiny projection neurons (MSNs), achieved through a viral expression of channelrhodopsin-2 in mice with regulatory elements for the dopamine D1 or D2 receptor. Excitation of the indirect-pathway MSNs elicited a parkinsonian state, distinguished by increased freezing, bradykinesia and decreased locomotor initiations. Activation of direct-pathway MSNs reduced freezing and increased locomotion (Kravitz, 2010)." A month prior to this Nature paper, Bass and colleagues from Wake Forest, described an optogenetic approach to controlling dopamine release (Bass, 2010).

Activating brain circuits by using both light and genetics has thus evolved from a science fiction dream into a true reality. The technique will likely be refined over the next decade and it will have tremendous potential to unlock important clues underlying the disease processes ultimately responsible for Parkinson's disease. Optogenetics may also open up novel therapeutic possibilities. We can thus conclude there is a bright future ahead for optogenetics, and there is much hope that this technology will help us shine a light on this common, and often disabling humanneurodegenerative condition.

Selected References
We refer the reader to both of these excellent references which describe optogenetics and also detail recent advances in the Parkinson's disease research arena.

Kravitz AV, Freeze BS, Parker PR, Kay K, Thwin MT, Deisseroth K, Kreitzer AC. Regulation of parkinsonian motor behaviours by optogenetic control of basal ganglia circuitry. Nature. 2010 Jul 29;466(7306):622-6.

Bass CE, Grinevich VP, Vance ZB, Sullivan RP, Bonin KD, Budygin EA. Optogenetic control of striatal dopamine release in rats. J Neurochem. 2010 Jun 8.

You can find out more about our National Medical Director, Dr. Michael S. Okun, by also visiting the Center of Excellence, University of Florida Health Center for Movement Disorders and Neurorestoration. Dr. Okun is also the author of the Amazon #1 Parkinson's Best Seller 10 Secrets to a Happier Life and 10 Breakthrough Therapies for Parkinson's Disease.

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