Prying minds with mind-blowing optogenetics

Did you know there was such a thing as optogenetics? The idea alone completely blows my mind:

"Optogenetics uses light to control neurons which have been genetically sensitised to light. It is a neuromodulation technique employed in neuroscience that uses a combination of techniques from optics and genetics to control and monitor the activities of individual neurons in living tissue to precisely measure the effects of those manipulations in real-time. The key reagents used in optogenetics are light-sensitive proteins." [Wikipedia]

The "light sensitive proteins" mentioned above are a family of proteins, called opsins, that are found in the photoreceptor cells of the retina. These proteins are responsible for converting light (photons) into electrochemical signals.

So, in layman terms, the idea behind optogenetics is that if we can deliver these opsin proteins into the neurons, making them sensitive to light, we can then use light to control the neurons themselves. This is used to understand the function of certain cell types in the brain. How do you deliver the proteins to the neurons? Using viral vectors, of course. When injected into the brain, the viral vectors infect the neurons, delivering the opsin genes. These genes make the neurons sensitive to light and can therefore be activated or silenced using optical fibers delivering light. It sounds very much like science fiction, but basically this enables researchers to control neurons using optical fibers.

Source: Lumencor

This optic stimulation is limited to very small areas of the brain. Not only that. The way neurons react to light depends on the frequency used to stimulate them. Animal studies have shown that light stimulation of the ventral segmental area can induce depressive-like behaviors at 20 Hz, whereas increasing to 30 Hz (in a different study) elicited antidepressant effects.

Because there's a whole family of opsin proteins, current research is aimed at understanding which ones work best depending on the experimental setting and circumstances. For example, different opsins can elicit neurons at different wave lengths, and when there's no overlap between the two spectra, two different opsin proteins can be used simultaneously to obtain two different outcomes on neural activity. Pushing this even further, genes coding for these proteins can be mutated to change their wave-length and frequency sensitivity and can be optimized for certain experimental settings.

Researchers use optogenetics to identify brain circuits that control emotions like fear, depression, and anxiety, and all the areas involved in those circuits. Previous methods included local lesions, pharmacological treatment, and electrophysiological studies, but these didn't give complete control on the temporal window like light stimulation does, which can activate or inhibit neurons at a very precise moment. It's fascinating stuff that I confess I don't completely understand myself as it is not my field, so I welcome the input from any experts out there willing to share their view and any literature recommendations!

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[1] Belzung C, Turiault M, & Griebel G (2014). Optogenetics to study the circuits of fear- and depression-like behaviors: A critical analysis. Pharmacology, biochemistry, and behavior, 122C, 144-157 PMID: 24727401