Considering Optogenetic Applications in Humans

 What if the solution to a problem could be solved with just the flip of a switch? With novel advancements in optogenetics, it just might be that easy.

Optogenetics is a relatively new technology that utilizes light to stimulate cells or neurons that have specialized light-sensitive ion channels. In the study done by Dr. Stiedl, optogenetic stimulation of the ventral tegmental area (VTA) was used to examine mechanisms of reward. Using optogenetic probe implantation, they were able to precisely stimulate laterodorsal tegmental nucleus cholinergic and gulatmatergic fibers in the VTA (Steidl, 2017).

Since light does not usually penetrate through the skull to the brain, most optogenetic interventions such as Dr. Steidls are highly invasive and require surgery to implant a fiber optic cable that directly inserts onto the brain.

To combat the invasiveness of the technique, researchers Dr. Xin Gong et al. have engineered a novel step-function opsin called SOUL which has ultra-high light sensitivity. This allows neurons in animals with SOUL mutations to be activated just by transcranial optic stimulation and does not require an invasive optic cable to be inserted. Further the step-function aspect of the technology allows ion channels to be open for up to 30 minutes after stimulation, allowing these animals to freely move around while the neurons remain activated. Perhaps most importantly is that SOUL worked with neurons in the lateral hypothalamus, one of the deepest regions in the mouse brain, as well as in the cortex in macaque monkeys (Gong, 2020).

Applying this clinically in humans could present incredible potential as a therapeutic for a variety of neurological and psychiatric disorders and could even serve as an alternative to deep brain stimulation, an invasive yet effective technique that has been used in attenuating some of the symptoms in motor neuron diseases such as Parkinson’s. However, the article by Drs. Adamcyzk  and Zawadzki illustrates the ethical concerns regarding the potential of optogenetic applications in humans due to its specificity and accuracy. For example, one study they found was able to implant a false memory in mice brains by means of contextual fear conditioning using optogenetics and not only succeeded in implanting the false memory but was able to do so without any form of communication. Other studies they cited demonstrated how optogenetics can treat memory loss, enhance memory, or improve memory consolidation. However, specifically in terms of using optogenetics in memory modification technologies, this powerful potential can also present neuroethical concerns, particularly regarding exploitation, authenticity, and exactly who should be qualified to receive these treatments (Adamcyzk and Zawadzki, 2020).

Taken together, optogenetics is an incredible tool in neuroscience and, if applied to human clinical trials, could present a viable treatment for a number of neurological disorders. However, although no human trials have taken place yet, it is never too early to consider the ethics of applying such a technique. Especially in terms of memory modification technologies, where exactly is the line drawn between necessary therapeutic and simply performance enhancement? And who decides? As optogenetics prove to be a more realistic therapeutic in humans, it is important to establish a sound infrastructure for optogenetic neuroethical standards as well.

Works Cited:

Adamcyzk, A.K., and Zawadzki, P. (2018, Oct. 17). The Memory-Modifying Potential of Optogenetics and the Need for Neuroethics. NanoEthics. 14, 207-225. https://link.springer.com/article/10.1007/s11569-020-00377-1.

Gong, X., Mendoza-Halliday, D., Ting, J.T., Bi, G., Desimone, R., Feng, G. (2020, Jul. 8). An Ultra-Sensitive Step-Function Opsin for Minimally Invasive Optogenetic Stimulation in Mice and Macaques. Neuron. 107(1): 38-51. https://www.cell.com/neuron/fulltext/S0896-6273(20)30239-7?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0896627320302397%3Fshowall%3Dtrue#%20.

Steidl, S., Wang, H., Ordonez, M., Zhang, S., Morales, M. (2017, Feb.). Optogenetic excitation in the ventral tegmental area of glutamatergic or cholinergic inputs from the laterodorsal tegmental area drives reward. European Journal of Neuroscience. 45(4): 559-571. https://pubmed.ncbi.nlm.nih.gov/27740714/.