Dr. Steidl, a professor at Loyola University Chicago, conducts research on cholinergic and glutaminergic inputs into the dopamine reward system in rats. In order to focus on specific neurons in brain nuclei, specifically the PPTg and LDTg, he needs to have the ability to elicit excitation in specific populations of neurons. Optogenetics is a technique that allows for such control. This technique relies on the use of viral vectors that introduce genes encoding for opsins, a light sensitive membrane protein, into specific neurons. The opsins are later stimulated by a particular wavelength of light to produce an action potential.
Although optogenetics is promising, its use in the clinical realm is limited. Genetic manipulation of humans is frowned upon and the relative control over these viral vectors is unknown. There is no guarantee that the gene of interest will not be incorporated into some other crucial gene. For now, it appears optogenetics will remain a technique used in research labs, and not in a treatment setting.
It an attempt to bypass the necessity of genetic manipulation, recent labs have been using pulsed infrared laser light to stimulate excitable cells. This approach relies on the change in membrane capacitance resulting from a transient change in temperature in the medium proximal to the membrane. A change in capacitance allows for the formation of depolarizing currents, thereby increasing the likelihood of an action potential. The consequences of this seemingly perfect design are manifested in cellular side effects. Infrared energy is damaging to other cellular processes and non specific.
A recent publication in the journal Neuron by Carvalho-de-Souza et al. presents a safer alternative to optogenetics. The researchers were experimenting with gold nanoparticles that have the capacity to absorb energy near infrared ranges. These gold particles can convert that high energy to localized heat, limiting the amount of damage done to the cell. As with most experiments, the researchers encountered some difficulty with localization of these nanoparticles because of their tendency to diffuse in solution. The problem was solved by conjugating the gold nanoparticles to ligands, such as antibodies or synthetic molecules. Ligands also allowed the introduction of high specificity, as they can be engineered to bind with specific ion channels. Now it appears that we have the ability to affect certain types of excitable cells by targeting specific ion channels without genetically modifying any genome.
Sources:
Carvalho-De-Souza, João L., Jeremy S. Treger, Bobo Dang, Stephen B.h. Kent,
David R. Pepperberg, and Francisco Bezanilla. "Photosensitivity of Neurons
Enabled by Cell-Targeted Gold Nanoparticles." Neuron86.1 (2015): 207-17. Web.
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