Looking at a Bright Future: Optogenetics in your Lab

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Have you heard about optogenetics yet? If not, you soon will. Optogenetics techniques are sweeping neuroscience research. Named as the Method of the Year in 2010 by Nature Methods, optogenetics techniques are becoming widespread.

The reason is clear: optogenetics offer the unprecedented ability to manipulate specific cells in real-time in freely behaving animals essentially by controlling a light switch. This allows for the dissection of intricate microcircuits that was previously impossible.  Specific brain regions and neuronal types can be turned on and off at will. The effect on animal behavior of activation of a specific neuronal circuit can be observed immediately. This is an exciting and far-reaching opportunity to fine-tune functional and neuroanatomical knowledge.

The technology began as the result of long-time collaborations between Drs. Edward Boyden and Karl Deisseroth, among others (Boyden 2011).  To better define the roles of individual neurons, these pioneers sought a way to drive or silence specific neurons embedded in intact brain circuitry.  They found the way using an ion channel expressed in the green algaChlamydomonas reinhardtii: channelrhodopsin-2 (ChR-2).  ChR-2 is a cation-selective ion channel that is directly light-gated.  In green alga, ChR-2serves to direct the alga to or from a light source to facilitate photosynthesis (Sineshchekov et al., 2002).  When inserted into neurons, ChR-2 mediates light-driven spiking (Boyden et al., 2005).  Viral transfection was first used to successfully express ChR-2 in neurons in vivo, thus opening the field of optogenetics to animal models (Arenkiel et al., 2007).

For in vivo use, an optical fiber is implanted into the brain for either acute or chronic use.  Once the light is turned on, the cells expressing ChR-2 will be activated as the channel depolarizes the cell.  Alternately, halorhodopsin expression is used to hyperpolarize a cell upon illumination, thus inactivating it at will (Tye and Deisseroth, 2012).  In many cases, this will shorten the time frame required for behavioral experiments, as intervention with optogenetics requires no “wash-out” period, as pharmacological manipulations would (Tye and Deisseroth, 2012)… View Original Article»

Dissecting the Neural Circuits Mediating Anxiety

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Neurostimulation as a tool for Basic Science and Medicine. 

Anxiety disorders are the single most-common class of psychiatric diseases, afflicting up to 28% of the adult population. Although human imaging studies have implicated the amygdala in anxiety, little is known about the functional role of individual microcircuits and distal circuits in terms of their individual contributions to anxiety. Optogenetics, the use of genetically-encodable, light-activated proteins that can be used to depolarize or hyperpolarize cell membranes, is a quickly-growing field. We developed optogenetic projection-specific targeting, electrophysiological and imaging techniques to parse the different circuit contributions, and we apply this multidisciplinary approach to provide a more complete view of how amygdala interactions with the rest of the brain can govern anxiety-related behaviors… View Original Video»

Video Source: Kavli Frontiers of Science

An On-Off Switch for Anxiety

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An On-Off Switch for Anxiety

Researchers discover a brain circuit that can instantly dampen—or exacerbate—anxiety in mice.

With the flick of a precisely placed light switch, mice can be induced to cower in a corner in fear or bravely explore their environment. The study highlights the power of optogeneticstechnology—which allows neuroscientists to control genetically engineered neurons with light—to explore the functions of complex neural wiring and to control behavior.

In the study, Karl Deisseroth and collaborators at Stanford University identified a specific circuit in the amygdala, a part of the brain that is central to fear, aggression, and other basic emotions, that appears to regulate anxiety in rodents. They hope the findings, published today in the journal Nature, will shed light on the biological basis for human anxiety disorders and point toward new targets for treatment.

“We want to conceptualize psychiatric disease as real physical entities with physical substrates,” says Deisseroth. “Just like people who have asthma have reactive airways, people with anxiety disorders may have an underactive projection in the amygdala.”…View Original Article»

Author: Emily Singer