Dr. Tsai is both professor and the director of the Picower Institute at MIT. Her research focuses on degeneration caused by Alzheimer’s; she recently found a way to reverse some of the effects of Alzheimer’s. Dr. Steidl is a behavioral neuroscientist that published an article on how cholinergic and glutamatergic neurons regulate the reward pathway. At first glance, it seems that the two studies have nothing in common; however, both studies utilized optogenetics in their research. Optogenetic is a genetic tool that stimulates neurons by light. This is done by genetically engineered organisms (through viral vectors), then opsin genes are injected into the areas of interest. You then will be able to stimulate or inhibit specific neurons through exposure to light (ncbi.nlm.nih.gov). One of the main benefits of optogenetic is the specificity allowed by this technique; it is very easy to modify the organism so the light will only activate the cells of interest.
Dr. Steidl wanted to see what is the role of cholinergic and glutamatergic receptors in regards to reward. It is known that cholinergic and glutamatergic responses from the laterodorsal tegmental nucleus (LDTg) are involved in the regulation of dopamine respond in the ventral tegmental area (VTA). Dr. Steidl used optogenetics to in two groups of mice, to selectively activate either cholinergic (ChAT-ChR2 mice) or glutamatergic (VGluT2-ChR2 mice) neurons in the LDTg area. The mice were placed in a 3-chamber apparatus, where one of the chambers was was light activated. When mice entered this room, the light would either stimulate the cholinergic or glutamatergic neurons (depending on which set of mice were used). It was found that the ChAT-ChR2 mice stayed longer in the light activated chamber and the VGluT2-ChR2 mice entered the light activated chambers more often but overall spent the same amount of time in the light paired chamber with the light unpaired chamber (but didn’t stay along). The results of this experiment show that cholinergic neurons are more responsible for the rewarding effects of an action while glutamatergic are more responsible for the reinforcement of a specific action. (steidl, 559 -570)
Dr. Tsai mention in her research many neurons in the brain fires at the gamma frequency (25-80 Hz); this frequency is important in higher level cognitive function. Patients with Alzheimer’s (neurological disorders) have reduced gamma activity throughout their brain. Dr. Tsai then decided to drill a small hole in the skull of mice (which were optogenetically modified) and then attached a fiber optic cable to the hippocampal region of the brain. The hippocampus was chosen because this was the region that is responsible for long-term memory storage. Then they flickered light through the fiber optic cable at 40Hz (gamma frequency). After one hour of the light therapy, it was found the 50 percent of all the beta-amyloid plaque was gone. It is known that microglial cells become inactive in patients with Alzheimer’s; microglial cells are important in the cleanup and repair of neural tissues. Dr. Tsai and her team hypothesized that optogenetic stimulation (at the gamma frequency) somehow stimulated the inactive microglial cells. Unfortunately, though the Beta-amyloid plaques return to normal levels if the light therapy isn’t given every 24 hours (scientificamerican.com)
These two studies are vastly different but use optogenetics. This show versatility of optogenetics how it can be used in a variety of situations.
Works Cited
Anne Trafton | MIT News Office. “Unique visual stimulation may be new treatment for Alzheimer's.” MIT News, 7 Dec. 2016, news.mit.edu/2016/visual-stimulation-treatment-alzheimer-1207.
“Bringing Gamma Back.” Radiolab, www.radiolab.org/story/bringing-gamma-back/.
Guru, Akash, et al. “Making Sense of Optogenetics.” International Journal of Neuropsychopharmacology, Oxford University Press, Oct. 2015, www.ncbi.nlm.nih.gov/pmc/articles/PMC4756725/.
Landhuis, Esther. “Uncovering New Players in the Fight Against Alzheimer's.” Scientific American, 20 Apr. 2016, www.scientificamerican.com/article/uncovering-new-players-in-the-fight-against-alzheimer-s/.
Steidl, Stephan, et al. “Optogenetic excitation in the ventral tegmental area of glutamatergic or cholinergic inputs from the laterodorsal tegmental area drives reward.” European Journal of Neuroscience, vol. 45, no. 4, 2016, pp. 559–571., doi:10.1111/ejn.13436.
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