Using photons as neurotransmitters to control neuron activity

Summary: Researchers present a new system that uses photons instead of chemical neurotransmitters to control neuronal activity.

Source: ICFO

Our brain is made up of billions of neurons, which are connected by forming complex networks. They communicate with each other by sending electrical signals, called action potentials, and chemical signals, called neurotransmitters, in a process called synaptic transmission.

Chemical neurotransmitters are released from one neuron, diffuse to others and arrive at targeted cells, generating a signal that excites, inhibits or modulates cellular activity. The timing and strength of these signals are crucial for the brain to process and interpret sensory information, make decisions, and generate behavior.

Controlling the connections between neurons would allow us to better understand and treat neurological disorders, rewire or repair dysfunctional neural circuits after they have been damaged, improve our learning abilities or expand our set of behaviors. There are several approaches to controlling neural activity.

One possible method is to use drugs that alter the levels of chemical neurotransmitters in the brain and affect the activity of neurons. Another approach is to use electrical stimulation applied to specific regions of the brain to activate or inhibit neurons. A third possibility is to use light to control neural activity.

Using photons to control neural activity

Using light to manipulate neural activity is a relatively new technique that has been explored in the past. It involves genetically modifying neurons to express light-sensitive proteins, ion channels, pumps or specific enzymes in target cells. This technique allows researchers to precisely monitor the activity of concrete populations of neurons with greater precision.

However, there are some limitations. It must be delivered very close to the neurons to achieve sufficient resolution at the synapse, as the light scatters into the brain tissue. Thus, it is often invasive, requiring external interventions. Moreover, the intensity necessary to reach the targeted cells can be potentially harmful to them.

To overcome these challenges, a team of ICFO researchers present in Natural methods a system that uses photons instead of chemical neurotransmitters as a strategy to control neuronal activity.

ICFO Montserrat Porta researchers, Adriana Carolina González, Neus Sanfeliu-Cerdán, Shadi Karimi, Nawaphat Malaiwong, Aleksandra Pidde, Luis Felipe Morales and Sara González-Bolívar led by Professor Michael Krieg with Pablo Fernández and Cedric Hurth, have developed a method to connect two neurons using luciferases, light-emitting enzymes and light-sensitive ion channels.

They developed and tested a system called PhAST -short for Photons as synaptic transmitters- in the roundworm Caenorhabditis elegans, a model organism widely used to study specific biological processes. Resembling the way bioluminescent animals use photons to communicate, PhAST uses luciferase enzymes to send photons, instead of chemicals, as transmitters between neurons.

Replace chemical neurotransmitters with photons

To test whether photons could encode and transmit the state of activity between two neurons, the team genetically modified the roundworms to have defective neurotransmitters, rendering them insensitive to mechanical stimuli. They aimed to overcome these flaws using the PhAST system. Second, they designed light-emitting enzymes, luciferases, and selected light-sensitive ion channels.

To track the flow of information, they developed a device that delivered mechanical stresses to the animal’s nose while, at the same time, measuring calcium activity in sensory neurons, one of the intracellular ions and messengers the most importants.

To be able to see photons and study bioluminescence, the team had previously designed a new microscope by simplifying a fluorescence microscope, removing all unnecessary optical elements such as filters, mirrors or the laser itself, assisted by machine learning to reduce noise. from external light sources.

The researchers then tested that the PhAST system worked in several experiments and was successful in using photons to transmit neural states. They were able to establish a new transmission between two unconnected cells, restoring neural communication in a faulty circuit.

They also suppressed the animals’ response to a pain stimulus, changed their response to an olfactory stimulus from attractive to aversive behavior, and studied the dynamics of calcium during egg laying.

These results demonstrate that photons can indeed act as neurotransmitters and enable communication between neurons and that the PhAST system enables the synthetic modification of animal behavior.

The potential of light as a messenger

Light as a messenger offers a wide scope for potential future applications. As photons can be used in other cell types and several animal species, this has broad implications for both basic research and clinical applications in neuroscience.

Using light to control and monitor neural activity can help researchers better understand the mechanisms underlying brain function and complex behaviors, and how different regions of the brain communicate with each other, providing new ways imaging and mapping of brain activity with higher spatial and temporal resolution. It could also help researchers develop new treatments and, for example, be useful in repairing damaged brain connections without invasive surgery.

However, there are still limitations to the widespread use of the technology, and further improvements in the engineering of bioluminescent enzymes and ion channels or in the targeting of molecules would make it possible to optically monitor neuronal function, noninvasively and with greater specificity. and precision.

About this neuroscience research news

Author: Alina Hirschman
Source: ICFO
Contact: Alina Hirschmann – ICFO
Picture: Image is credited to ICFO

Original research: Access closed.
“Neural engineering with photons as synaptic transmitters” by Montserrat Porta-de-la-Riva et al. Natural methods

Abstract

Neural engineering with photons as synaptic transmitters

Neural computation is achieved through connections of individual neurons in a larger network. To expand the repertoire of endogenous cellular communication, we developed a synthetic photon-assisted synaptic transmission (PhAST) system.

PhAST is based on luciferases and channelrhodopsins which allow the transmission of a neuronal state through space, using photons as neurotransmitters.

PhAST overcomes synaptic barriers and rescues behavioral deficit of glutamate mutant with calcium-triggered conditional photon emission between two neurons in the Caenorhabditis elegans nociceptive avoidance circuitry.

To demonstrate versatility and flexibility, we generated de novo synaptic transmission between two unconnected cells in a sexually dimorphic neural circuit, suppressed the endogenous noxious response through activation of a rhodopsin anion channel, and switched attractive behavior to a aversive behavior in an olfactory circuit.

Finally, we applied PhAST to dissect the calcium dynamics of the temporal pattern generator in a motor circuit for spawning. In summary, we have established photon-based synaptic transmission that facilitates modification of animal behavior.