Our brain is made up of billions of neurons that are connected to each other forming complex networks. These neurons communicate through a process called synaptic transmissionin which electrical signals, action potentials, and chemical signals are sent through neurotransmitters.
Chemical neurotransmitters are released from one neuron, diffuse to the others, and reach target cells generating a signal that excites, inhibits, or modulates cell activity. The timing and strength of these signals are crucial for the brain to process and interpret sensory information, make decisions, and generate behavior.
A system that uses photons instead of chemical neurotransmitters as a strategy to control neuronal activity is presented.
Controlling the connections between neurons would allow us to better understand and treat neurological disorders, rewire or repair faulty neural circuits after they have been damaged, improve our learning abilities, or expand our set of behaviors.
There are several methods for control neural activity. The use of drugs is the most common alternative, which makes it possible to alter the levels of chemical neurotransmitters present in the brain and affect the activity of neurons. Another option is to electrically stimulate specific areas of the brain to activate or inhibit neurons. But there is a third possibility: use light.
Light to control neural activity
The manipulation of neural activity by light is a relatively new technique that has been explored in the past. This technique involves genetically modify neurons to express light-sensitive proteins and ion channels and specific pumps or enzymes in the target cells.
Although this method allows researchers to control the activity of particular groups of neurons with greater precision, there are still some limitations. Because light is scattered in brain tissue, it must be delivered very close to neurons to achieve sufficient resolution at the synapse level. This involves using often invasive techniques, and requires external interventions. Furthermore, the intensity that is needed to reach the target cells can potentially be harmful to them.
Researchers have developed a method to connect two neurons using luciferases (light-emitting enzymes) and photosensitive ion channels
Now, researchers from the Institute of Photonic Sciences (ICFO) publish in the journal Nature Methods a system that uses photons instead of chemical neurotransmitters as a strategy to control neural activity. Specifically, his method allows connecting two neurons using luciferasas (enzymes that emit light) and photosensitive ion channels.
The team, led by Professor Michael Krieg and with Montserrat Porta As the first author, she has developed and tested a system, called PASTin the nematode Caenorhabditis elegansa model organism widely used to study biological processes.
‘Caenorhabditis elegans’ nematode, the worm species used in the study. / Zeynep F. Altun
Just as bioluminescent animals use photons to communicate, the developed method uses synthesized enzymes to send photons, rather than chemicals, as transmitters between neurons.
To see if it was really possible to use photons to encode and transmit the state between two neurons, the team first genetically modified the worms by altering their neurotransmitters in such a way that they were insensitive to mechanical stimuli. The objective was to see if, with the designed system, these sensory alterations could be reversed.
Second, the researchers synthesized luciferases and selected light-sensitive protein ion channels, called channelrhodopsins.
Follow the activity of calcium
Finally, they developed a device that delivered mechanical stimuli to the tip of the worms’ noses, simultaneously measuring the activity of the nose. soccer (one of the most important intracellular ions and messengers) in sensory neurons. This allowed them to follow the flow of information.
In order to see the photons and study bioluminescence, the team previously designed a specific microscope assisted with machine learning. They simplified a fluorescence microscope by removing some common optical elements such as filters, mirrors, or the laser itself, and completely covered it to eliminate external light contamination.
With this technique, a neural connection has been restored, the animal’s response to painful stimuli has been suppressed, and behavior from attraction to aversion has been changed.
The researchers also designed various experiments who have managed to establish that photons can, in fact, transmit neural states. In one of them, a new communication between two neurons previously unconnected, restoring a neural connection in a faulty circuit.
Also suppressed the animal’s response to stimuli painful, they changed their behavior going from attraction to aversion in response to an olfactory stimulus and studied the calcium dynamics during egg laying.
The results show that photons can act as neurotransmittersallowing communication between neurons, and that the PhAST system allows the synthetic modification of animal behavior.
The potential of light as a messenger
As light can be used in more cell types and in more animal species, it offers great potential for a wide range of applications, from basic research to clinical applications in neuroscience.
Controlling and monitoring neural activity using light can help the scientific community, for example, to better understand the mechanisms underlying brain function and complex behaviors, or to determine how different brain regions communicate with each other.
Controlling and monitoring neural activity using light can help to better understand the underlying mechanisms of brain function
It can also bring new ways of scan and map brain activity with higher spatial and temporal resolution. Furthermore, it may be useful in the future to develop new treatments to repair damaged neural connections without the need for invasive surgeries.
The path to follow in the future is aimed at improving the engineering of bioluminescent enzymes, ion channels or target molecules, which would make it possible to control neuronal function optically, non-invasively, and with greater specificity and precision.