They can control neural activity with photons

Our brain is made up of billions of neurons that connect to each other forming complex networks. These neurons communicate through a process called synaptic transmission, in which electrical signals, action potentials, and chemical signals are sent via neurotransmitters.

Chemical neurotransmitters are released from one neuron, diffuse to others and reach target cells generating a signal that excites, inhibits or modulates cell activity. The timing and strength of these signals is 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 to control neural activity. The use of drugs is the most common alternative, which allows altering the levels of chemical neurotransmitters present in the brain and affecting 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: using light.

Light to control neural activity

Manipulation of neural activity by light is a relatively new technique that has been explored in the past. This technique involves genetically engineering neurons to express light-sensitive proteins and ion channels and specific pumps or enzymes in target cells.

Although this method allows researchers to track the activity of certain groups of neurons more precisely, there are still some limitations. As light is scattered in brain tissue, it must be delivered very close to neurons to achieve sufficient resolution at the synapse level. This involves the use of techniques that are often invasive and require external interventions. Furthermore, the intensity required to reach 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 at the Institute of Photonic Sciences (ICFO) publish in the journal Nature’s 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 luciferases (enzymes that emit light) and photosensitive ion channels.

The team, led by Professor Michael Krieg and with Montserrat Porta as the first author, developed and tested a system, called PhAST, on the nematode Caenorhabditis elegans, a model organism widely used to study biological processes.

Just as bioluminescent animals use photons to communicate, the method developed uses synthesized enzymes to send photons, rather than chemicals, as transmitters between neurons.

Replacing chemical neurotransmitters with photons

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 so that they were insensitive to mechanical stimuli. The aim was to verify whether, with the designed system, these sensory changes could be reversed.

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Second, the researchers synthesized luciferases and selected light-sensitive protein ion channels called channelrodopsins.

Keep track of calcium activity

Finally, they developed a device that delivered mechanical stimuli to the tip of the nose of the worms, simultaneously measuring the activity of calcium (one of the most important ions and intracellular messengers) in the sensory neurons. This allowed them to follow the flow of information.

To see photons and study bioluminescence, the team previously designed a dedicated microscope aided by 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 contamination from outside light.

With this technique, a neural connection was restored, the animal’s response to painful stimuli was suppressed, and behavior from attraction to aversion was changed.

The researchers also designed several experiments that managed to establish that photons can, in fact, transmit neural states. In one, a new communication was established between two previously disconnected neurons, restoring a neural connection in a faulty circuit.

They also suppressed the animal’s response to painful stimuli, changed its behavior from attractive to aversive in response to an olfactory stimulus, and studied calcium dynamics during egg laying.

The results obtained show that photons can act as neurotransmitters, allowing 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 researchers, for example, better understand the mechanisms underlying brain function and complex behaviors, or determine how different regions of the brain communicate with each other.

It may also provide new ways to scan and map brain activity with greater 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 surgery.

The way forward in the future is to improve the engineering of bioluminescent enzymes, ion channels or target molecules, which would allow controlling neuronal function optically, non-invasively and with greater specificity and precision.

Reference:

Montserrat Porta-de-la-Riva et al. “Neural engineering with photons as synaptic transmitters”. Nature’s Methods, 2023

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