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Shining light on the brain, ME-Optogen

We said it in the presentation post, this blog is also about science. 
Today I'll talk about a recent research project I carried out in Paris in the Emiliani Lab from 2017 to 2019, which was financed by the European Union, within the framework of the Marie Skłodowska Curie actions. The title of the project is: ‘Micro-endoscopes for in-depth high-resolution optogenetics’, its acronym ME-Optogen. In this short article I’ll try to guide you, in a very simple and informal way, through the motivations behind this work and its main results. More articles may follow to better explain some concepts I’ll have no time to explain here.
Despite the enormous progress in research and technology of the past decades, we still have a very hard time understanding how the brain works. The reason is the extreme complexity of the human brain, in which every neuron (we have several billions) is connected to many others, forming an intricate network of connections that is almost impossible to map completely. Here a video that gives an idea of the complexity of the neuronal connections in the human brain. 
It is then not all about connections. Neural activity flows throughout the brain network in a way that is impossible to predict on the basis of the bare connections. Even if we know that two neurons are anatomically connected, that does not mean that the same information flows from one to the other, because activity of other neurons is capable to modulate such flow at all times. It is this activity flow through the network that is at the basis of our comprehension of the external world, our response to external stimuli, our thoughts and memories.
The objective of ME-Optogen was to make a small technological step and develop new research methods that could ease future studies of the brain.
I am a physicist by training and I was working on very different subjects before starting my postdoc in Paris. As the many followers of this blog know, we, the authors, are a bunch of physicists that all met together in Barcelona when we were PhD students. After my PhD I felt the pressing need of changing topic and starting something different. I then decided to stop studying nanoparticles (the subject of my PhD thesis, you find it here if you really want to read it) and apply what I knew (basically aligning laser beams and setting up microscopes) to the study of the brain.
Now the question at this point was: ‘what was there that I could do, with my training in physics and optics, that could be useful for the study of the brain?’ Well fortunately, people had previously discovered that, by genetically manipulating neurons, it is possible to make them sensitive to light in a way that we can record videos of their activity as well as induce neural activity by using light. This combination of genetics and optical techniques is today called ‘Optogenetics’. Here a video explaining the concept. So yes, if you are doing optics and you’re an expert in using laser light, there is something you can do in the field of neuroscience. You could use your ability to guide light from a point A to a point B to induce and read out neural activity in a neural network. This is why today the use of light is becoming more important for the study of the brain with each passing day.
With ME-Optogen we developed new optical techniques that can be used for a better study of neural circuits in the brain. Particularly, we focused on two challenges that limited the use of optics in neuroscience. First, if you want to really understand how different neurons communicate, you need a way to precisely activate with light only the neurons you want to track, and not the others. This was the subject of my first work in the Emiliani Lab that was published last year. Second, reaching deep brain regions with optical techniques is today very challenging. For the same reason you cannot see clearly through the fog, a microscope cannot really see neural activity after a certain depth in the tissue. This is why we need endoscopes to reach hidden regions of our bodies. In the second work of my postdoc, also published, we extended advanced optical techniques to a micro-endoscope that will be used to reach deep regions of the brain in a minimally invasive way.
It took two years and a lot of work by many people (especially in the Emiliani Lab) to reach these targets. As a result, today we have an optical system that we can finely control that is suitable for the precise study of many different neurons in a large volume of the brain. In the future, we plan to use it, with further developments to shed more light on complex brain circuits that today we still cannot understand. 

This is just a small step towards the ultimate objective that thousands of researchers across the world are today pursuing: decrypting the neural code. However, progress in science is often made by small steps and the contribution of many different people, which prepares the ground to a major discovery that once every many decades completely changes a research field. ME-Optogen is definitely not one of these major discoveries, but it produced new tools that researchers could use to approach one day a major discovery.

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