Skip to main content

Development of flash photolysis for deep uncaging in vivo and high throughput characterisation of neurotransmitter gated ion channels in drug discovery

Article Category

Article available in the folowing languages:

Advancing the method of photolysis for neuroscience

Studying physiological signalling events requires sensitive experimental techniques. An EU consortium optimised the method of photolysis for characterising neurotransmitter-gated ion channels in vivo.

Digital Economy

The experimental technique of photolysis utilises ‘caged’ precursor molecules that carry a photo-activatable group and require photon absorption in order to become activated. Caged substances range from ions and second messengers to neurotransmitters, and using this technique it is possible to precisely control in space and time the application of an experimentally applied signal molecule. This technique is providing new avenues of understanding into neurological disorders and drug delivery methods. A European consortium designed the project Photolysis to optimise the photolysis technique for neuroscience and cell physiology. Partners worked specifically on the photochemistry of two-photon excitation which led to the award of two patents. Ten new probes were also developed and significant improvements were made in the sources available for excitation, as well as in the spatial and temporal modification of the excitation light. The method was refined so that it could ultimately be applied in drug discovery. By modifying the spatial distribution of excitation in full-field microscopy, the Photolysis research project was successful in combining uncaging capabilities with optical means. The photolysis technology was also adapted to patch clamp systems providing a unique feature for investigating neurotransmitter function in vivo. Photolysis researchers thereby studied the modification of neural network discharge by transplanting in vivo fibroblasts over-expressing ion channels. The photolysis technology was also used to evaluate the behaviour of Parkinsonian rats following transplantation of cells at the globus pallidus interna (GPi) part of the brain. Project deliverables constitute invaluable tools for neuroscientists wishing to study neurotransmitter function in vivo, characterise drugs acting on various receptors and even evaluate the effect of cell replacement therapies.

Discover other articles in the same domain of application