Optogenetic Application: Mental Illness
Highly
prevalent and widespread, mental illness affects millions of people throughout
the world. With countless different treatment options and drug types, it has
become increasingly more difficult to determine the most effective course of
action when faced with a patient suffering from a mental illness.
Anti-depressant and mood stabilizing drugs often come with side effects, and
necessitate cognitive or behavioral adjustment therapy in order to prevent
relapse. Dr.
Stephan Steidl recently gave a presentation to my neuroscience seminar class on the newly developing technique
of optogentics, and sparked my interest in how it poses what could potentially be a breakthrough
treatment in both Depression and Schizophrenia by addressing their associations
with dopamine production. Evidence
suggests that depression is correlated with dopamine production below normal
functioning levels. In conjunction, it is thought that people suffering from
schizophrenia produce above normal functioning levels of dopamine. Until now,
there has not been a highly specified means to increase or diminish these
levels of dopamine production. Optogenetics, however, allows for the use of
light as a means to activate just one type of neuron without highly altering
the surrounding neurons, providing specificity not possible with extracellular
electrical manipulation.
The Development and Application of
Optogenetics written by
Lief Fenno, Ofer Yizhar, and Karl Deisserouth depicts the process by which this
highly specific neuronal excitation occurs. In order for neurons to be receptive
to the light, channelrhodopsin-2 (ChR2), a light-gated cation channel receptive to blue light, must be
transfected onto the membrane of the neurons of interest. Eventually, the
cation channel will establish itself down the axon to the neuron terminal.
Light can then be administered through an optic probe, depolarizing the ion
channel causing it to open and allow an influx of cations into the neuron. As a
result, the neuron transitions to an excited state prompting it to release an
action potential. If such a process is applied to dopamine neurons, then the
described action potential could cause a release of dopamine from the terminal
of the neuron. In theory, the depressed, dopamine poor brain would then start
experiencing higher levels of dopamine and thus a pacification of the symptoms
of depression. This process would not be a cure all end to depression, however,
it poses unprecedented means by which depressed patients, unresponsive to
antidepressant medications, could be helped. After hearing Dr. Steidl present on this work, I applied and was accepted to join his lab.
Optogenetic neuronal control in schizophrenia, written by Ave Peled, further applies these optogenetic techniques to schizophrenia. Peled points out that in order for these neuronal targeting techniques to be successful, they must target the neuron circuits: "known to be relevant for schizophrenia, involved in cognitive brain functions that are disturbed in schizophrenia, and relevant to alleged neuronal network mechanisms that are presumably damaged or malfunctioning in schizophrenia (Peled)." The prefrontal cortex is the brain region most strongly associated with the preceding conditions. Capable of communicating with the rest of the brain, optogenetic control of the prefrontal cortex neurons would correlate to control of the connectivity balance throughout the brain. As a result, dopamine levels in schizophrenic patients could be regulated. Pending further research to apply such techniques in mammalian systems, optogenetics clearly posses the ability to revolutionize the treatment of mental health disorders through scientific breakthrough.
References
Fenno, Lief, Yizhar, Ofer and Deisseroth, Karl. "The Development and Application of Optogenetics." - Annual Review of Neuroscience, 34(1):389. N.p., July 2011. Web. 14 Oct. 2015.
Optogenetic neuronal control in schizophrenia, written by Ave Peled, further applies these optogenetic techniques to schizophrenia. Peled points out that in order for these neuronal targeting techniques to be successful, they must target the neuron circuits: "known to be relevant for schizophrenia, involved in cognitive brain functions that are disturbed in schizophrenia, and relevant to alleged neuronal network mechanisms that are presumably damaged or malfunctioning in schizophrenia (Peled)." The prefrontal cortex is the brain region most strongly associated with the preceding conditions. Capable of communicating with the rest of the brain, optogenetic control of the prefrontal cortex neurons would correlate to control of the connectivity balance throughout the brain. As a result, dopamine levels in schizophrenic patients could be regulated. Pending further research to apply such techniques in mammalian systems, optogenetics clearly posses the ability to revolutionize the treatment of mental health disorders through scientific breakthrough.
References
Fenno, Lief, Yizhar, Ofer and Deisseroth, Karl. "The Development and Application of Optogenetics." - Annual Review of Neuroscience, 34(1):389. N.p., July 2011. Web. 14 Oct. 2015.
Peled Avi, Optogenetic neuronal control in schizophrenia, Medical Hypothesis, Volume 76, Issue 6, June 2011, Pages 914-921, ISSN 0306-9877, http://dx.doi.org/10.1016/j.methy.2011.03.009.
http://www.healthcommunities.com/schizophrenia/causes.shtml
Image
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http://web.stanford.edu/group/dlab/media/layout/frontrat.png
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