Optogenetics: An all powerful revolutionary technique?

 

Optogenetics is a new form of stimulating and controlling cells in the living tissue. Research is advancing in ways that we have not thought imaginable just mere years ago. While we already have a myriad of neuroimaging methods, optogenetics has managed to sweep the world of science. As soon as it appeared on the horizon, researchers from all over the world were able to see the massive advantages this technique will bring. Optogenetics is managing to foster many discoveries in research. This is the reason why the method has gained so much popularity in such a short span of time.

Optogenetics

Optogenetics

What is optogenetics?

In the recent years, scientific research has been stuck in the same old place. No matter how much the researchers tried, how many hours they spent in their laboratories, discoveries were halter. Scientists were finding certain things but it became rarer and rarer to hear about a “cause and effect” discovery. The research focused on correlation and comparing things to one another. This did not promote any type of scientific progress. Questions still remained questions. Scientists were still not able to properly treat various neurological and psychiatric diseases. Treating aside, in many cases, the diagnosis of these diseases was not timely either. Scientists did not have the answers and the technology was failing.

Many researchers put forward various initiatives in an attempt to understand everything there is to understand about the brain. Scientists organized and based The Human Brain Project specifically in an attempt to stimulate and compute the entire brain. And yet, to this day, we have no way of seeing the complex network of intricately connected neurons, their electrical signals, and the released neurotransmitters. How amazing would it be to be able to understand the messages that each neurotransmitter sends to the brain and follow each of the pathways for each of the neurotransmitters?

In order to be able to progress a little bit with regards to our knowledge of neuroscience, we need to look at a single cell.  Looking at a single neuron is quite ambitious since we know that, for example, electrophysiological techniques are not able to accomplish that. Maybe in organisms that do not have such complex system as ours, it would be possible. The brains of mammalians, though? The nervous system of humans and our similar animal counterparts is so intricate; we haven’t managed to look at a single neuron yet. Event-related potentials and EEG are able to pick up the entire network of neurons that are firing in a similar fashion, but a single cell?

Apart from just picking up a single neuron, scientists have to consider the time scale. Neurons fire in such a fast fashion that the signal in various millisecond points can make a big difference. No, scientists considered measuring a single cell virtually impossible. Scientists saw the potential as early as the 70’s with prominent figures saying that control over one cell will manage to speed up the discovery progress tremendously. Optogenetics has managed to do just that.

Optogenetics is, essentially, a biological technique. It uses light in order to have control over neurons in living matter. These neurons are manipulated beforehand and they can display ion channels that are sensitive to light.

Quick history of optogenetics

  • 1971: Oesterhelt & Stoeckenius disover that bacteriorhodopsin is able to behave as if it was an iron pump. Apart from that, if they applied light photons to it, it activated very fast. (1)
  • 1977: Matusno-Yagi & Muhokata discovered the same thing for halorhodopsin
  • 1979: According to Francis Crick, the major neuroscientific obstacle is the inability to control a single cell at once. He mentions that other cells have to be left as they are and the control only exhibits over one single cell. (1)
  • The 80’s: Crick mentions that we might be able to use light to control one single cell. At this point in time we do not have the technology to do that.
  • 2002 Hegemann, Nagel and others say that channelrhodopsin reacts in the same way as bacteriorhodopsin and halorhodopsin when light photons are applied to it.
  • 2005: neurons respond specifically to light when introducing a microbial opsin gene.
  • 2005: Karl Deisseroth & Ed Boyden publish a Nature Neuroscience paper – beginning of optogenetics
  • 2010: aforementioned halorhodopsin, bacteriorhodopsin, and channelrhodopsin are able to activate and inactivate neurons very fast. They are able to do so in response to different light colors. (1)

What is so cool about optogenetics?

Optogenetics is a technique that is so precise, it is able to control different events within specified cells at known times. Neuroscientists and biologists worldwide were dreaming of this type of precision when it comes to neurons.

Optogenetics manages to combine genetic and optical methods into one. That is what allows for such an accuracy with measuring one single neuron.

How does optogenetics work?

Scientists make specific neurons that are later on able to express proteins that are sensitive to light. In simple words, scientists will later shine a light on these neurons.  If they do so at the right frequency, they are able to control the neurons. Researchers are now able to either activate or inhibit the function of the neuron – that controls the action potentials. They are able to change the pathways of these neurons as well. Again, and this cannot be said enough, achieving this type of precision is absolutely crucial at this stage of neuroscientific and biological research.

New advancements in optogenetics

Once the scientists realized how beneficial the technique really is, they busied themselves to create ways to make the method even more useful. It happened gradually and that’s why optogenetics is really coming to the light (pun intended) now and not before. The possibility of using light for manipulating single cells was brought up a long time ago, however, scientists needed to bring other technology up-to-date for this method to work successfully.

Optogenetics

Optogenetics

Nowadays we are able to target specific subtypes of neurons via the use of specifically engineered proteins. Scientists have also developed various probes that measure the calcium found inside the cell, imaging for synapses and membrane voltage. Apart from that researchers developed different proteins that are able to turn the neurons on and off with different time-scales by using light in various ways.

Optogenetics and the brain

Scientists use optogenetics tools in many different parts of the brain.

Researchers used optogenetics to control behaviors that are associated with the sense of smell in the brain. Optogenetics was also successful in showing how and when the processing of smell happens in the brain.

Optogenetics tools were able to recover activity associated with hearing in deaf monkeys by manipulating the spiral ganglion.

Researchers always saw amygdala as the seat for the fight, flight or freeze concept. Optogenetics is able to regulate and control the beginning of the fear formation in the brain. They were able to make affected monkeys display the fight, flight or freeze behaviors.

Scientists were also able to produce action potentials in the prefrontal cortex with the help of optogenetics and excite and inhibit cholinergic neurons in the nucleus accumbens. Cholinergic neurons are neurons that are very vulnerable as we have seen in the progression of Alzheimer’s disease so it’d be very interesting to see whether optogenetics is able to turn on and off the neurons associated with the progression of certain diseases.

Optogenetics and diseases

Scientists use optogenetics tools for therapeutic purposes in certain well-known diseases. They’ve managed to show treatment potential after controlling axons for certain neurons associated with Parkinson’s disease.

Researchers also used optogenetics in research of Huntington’s disease were they controlled different GABA neurons and saw the potential for behavior improvement in Huntington Disease patients.  Scientists were also able to reduce activity for epileptic seizures via the use of optogenetics tools. In regards with Alzheimer’s diseases scientists were able to pin-point a pathway that could effect the aggregation of amyloid-beta peptide – an important bio-marker for the disease. Researchers were also able to encourage recovery after stroke by controlling neuronal activity in the primary motor cortex.

In regards with Alzheimer’s diseases scientists were able to pinpoint a pathway that could affect the aggregation of amyloid-beta peptide – an important biomarker for the disease. Researchers were also able to encourage recovery after stroke by controlling neuronal activity in the primary motor cortex.

Advantages of Optogenetics

As mentioned before, the ability to precisely control one single cell at a specific time during a specific event is a huge benefit of optogenetics. Optogenetics is being used for investigating for many things in neuroscience now. Scientists are looking at individual synapses, neurons, brain functions. Apart from that, researchers can now look into disease models via using animals. Researchers are also able to do more cause and effect studies due to the fact that they are able to turn neurons on and off and see specifically what they do. Optogenetics is allowing scientists to look at complex functions of the nervous system and translate them into understanding the external behaviors and cognition.

Optogenetics

Optogenetics
by Julie Pryor

With the advancement of optogenetics, scientists are trying and succeeding in discovering new opsins that they can use with the technique.

Neuroscientists are not the only ones benefiting from the development of optogenetics. Molecular and cell biologists, botanists, structural biologists, microbiologists, biophysicists and many others are using the technique on a daily basis in their laboratories as well. Taking this into account, we can see how optogenetics has managed to inhibit the majority of the scientific fields. Apart from that it has created a nice collaboration and convergence between the fields. Looking into various historical examples we can see that when prominent scientific fields converge and work together for a similar goal – that’s when the majority of advancements in science are made.

Disadvantages of Optogenetics

No technique is perfect, of course. Many have various drawbacks in regarding to their design and the functions that they display.It is not an ideal method either even if many scientists tend to believe so.

We know that various neurons are particularly responsive towards light via the use of optogenetics. Because of this, the light can make the neurons respond in a way that is not identical to how they respond physiologically by themselves. It’d be interesting to be able to record neuronal activity at the same time as using optogenetics to, perhaps, eliminate that factor.

This activation and inactivation in neurons could drive the cells to turn to neuroplasticity that wouldn’t have happened otherwise. This could potentially lead to results that will not be able to be generalized to a bigger population.

Apart from that, the optogenetics tools are not able to turn on various subtypes inside of the population that the scientists have genetically engineered. This is one of the main goals in advancement of optogenetics now, to find a way to be able to induce even more precision into the technique.

There are many more problems that people can find with optogenetics, however, we cannot disregard the major scientific advancements happening at this moment because of it.

Future directions

Optogenetics

Optogenetics
by Julie Pryor

Yes, as mentioned before, optogenetics needs improvement. Optogenetics in itself has the potential to be used in humans and help with preventing, diagnosing and treating major neurological and psychiatric diseases. Scientists already used optogenetics tools on mammals who were moving freely so it’s a matter of time and dedication before we can safely use these tools on humans as well. Before that, of course, we need to look for the solutions of the problems and limitations mentioned beforehand. Hopefully, one day soon, optogenetics will be the method everybody wants it to be – the perfect way of measuring everything in the brain. Science moves in unexpected direction. Perhaps, if optogenetics doesn’t deliver, another method will come along soon enough.

References

Deisseroth K. Optogenetics. Nat Methods. 2011;8(1):26–9.

Häusser M. Optogenetics: the age of light. Nat Methods [Internet]. 2014;11(10):1012–4. 

Vann KT, Xiong ZG. Optogenetics for neurodegenerative diseases. Vol. 8, International Journal of Physiology, Pathophysiology and Pharmacology. 2016. p. 1–8.

 

 

Valerie is a psychology student who is trying to pursue a career in Cognitive Neuroscience. She is passionate about the brain and finds it fascinating. She loves learning about new discoveries and research that is going on in the world of psychology and neuroscience. One day she hopes to contribute to the scientific community!