Research on microorganisms is helping scientists and researchers unveil new mysteries of human physiology and pathology, as well as diagnose and treat a variety of diseases and disease-causing processes. Recently, another microorganism — Chlamydomonas — helped scientists at Stanford University in understanding the functioning and mechanism of electrochemical signaling in promoting higher mental activities like thought processing, formation, consolidation and recall of memories and logical behavior. Likewise, the organism also helped to explain how certain aberrations in the normal functioning of brain cells may contribute to diseases like Parkinson’s disease and schizophrenia.
Background of research:
Green algae, or Chlamydomonas, are classified as light sensitive species (due to presence of a special protein — known as channelrhodopsin, which responds to light by propelling the organism towards a light source. Chlamydomonas, like all other green plants, are capable of synthesizing their own food through the process of photosynthesis using sunlight as an integral energy source.
Scientists from University of Texas Health Science Center at Houston first discovered the mechanism responsible for the light-chasing behavior of Chlamydomonas in 2002. John Spudich led the research team with renowned scientists like Kwang-Hwan Jung and Oleg SIneshchekov. The research scientists observed that upon exposure to light, channelrhodopsin is converted into electric current that allow it to transverse to the eye-spot and generate positive flow of electrical charges that steer the movement of flagellates (motility organelles for Chlamydomonas) in the direction of light.
Spudich, the biophysical chemist from UT Health Science Center invested decades in research to learn how light affect the swimming behavior of different microorganisms and how light sensitive receptors contribute to this function. He explained his research interest in Chlamydomonas in these words:
“My interest in Chlamydomonas was derived from my interest in the basic principles of vision. That is, the molecular mechanisms by which organisms use light to obtain information about their environment.”
He further added:
I have long been fascinated with how microorganisms ‘see’ the world and started with the simplest—bacteria with light-sensitive movements (phototaxis), followed by phototaxis in more complex algae. Our focus throughout has been on understanding the basic biology of these phenomena.”
Details of research:
Research by Spudich and other investigators at UT Health Science Center explained the basic survival behavior of various microorganisms and scientific explanation of the light sensitivity in organisms like Chlamydomonas. However, little was expected that over time, this development would also contribute to understanding essential brain functioning.
The research team from Stanford University utilized the findings discovered by Spudich in initiating preliminary studies to devise a technology that can selectively control the brain receptors and circuits of laboratory animals.
The Stanford team developed a switch that was controlled by light in order to control activation of brain cells. The decision to utilize light as a reflex was based on the fact that light controls most biochemical, neural and electrical mechanisms in nature; however, since neurons are inherently not sensitive to light, it was decided to implant a light sensitive molecule in the brain that can control the brain cells (that are being activated by light reflex).
The choice of such a molecule was really challenging until research by Spudich and another research by German scientists (Georg Nagel, Peter Hegemann and Ernst Bamberg) suggested that specialized proteins are responsible for conducting electric current in a variety of other animals as well besides algae.
The research team under Karl Deisseroth, Feng Zhang and Edward Boyden employed genetic engineering techniques to introduce light sensitive algal proteins in the brain cells of rats and mice in 2004. Extensive experimentation reveled that light sensitive proteins stimulated the neurons in the rats and mice by promoting electrochemical signaling and processes to achieve desired results instead of mere light chasing behavior.
This experimentation introduced the new concept of optogenetics- that can be explained as “the combination of genetics and optics to control well-defined events within specific cells of living tissue.”
The team also developed other generalizations like:
- Manipulation of light sensing proteins to stop the electrochemical signaling and turn off the desired neurons.
- Use of a laser bound fiber cable to introduce light to the targeted neurons of experimental subjects.
- Insertion of light sensing proteins in different parts of brain to assess the response of light on electrochemical signaling of different neurons.
- Controlling the expression of genes.
“The brain is a mystery, and in order to solve it, we need to develop a great variety of new technologies. In the case of optogenetics, we turned to the diversity of the natural world to find tools for activating and silencing neurons—and found, serendipitously, molecules that were ready to use.”
Future work and practical implications of optogenetics:
Currently a large amount of research and development is under way to study the optogenetical basis of different diseases like neurodegenerative disorders (Parkinson’ disease, Alzheimer’s disease) and other psychiatric conditions like schizophrenia, obsessive compulsive disorder, depression, stroke, pain disorder and other similar conditions.
‘What excites neuroscientists about optogenetics is control over defined events within defined cell types at defined times—a level of precision that is most crucial to biological understanding even beyond neuroscience. And milliscale-scale timing precision within behaving mammals has been essential for key insights into both normal brain function and into clinical problems, such as parkinsonism.”
Spudich from UT Health Science Center expressed his views in these words:
“The development of optogenetics is yet one more beautiful example of a revolutionary biotechnology growing out of purely basic research”
A number of other disciplines like physics, electrical engineering, microbiology and genetic engineering also helped tremendously in the evolution and development of concepts of optogenetics- which is also now an integral part of advanced brain research via Advancing Innovative Neurotechnologies (BRAIN)