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When light is a switch: Nanophotodiodes for studying neuronal activity

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A new study by SISSA takes a novel approach, The technique used can activate individual nerve cells with pulses of light. This targeted, non-invasive approach can be used for basic research on the nervous system and the development of innovative treatments for neurological disorders

A beam of light that modulates the activity of a single neuron in real time: this is how innovative nanophotodiodes work, the subject of a new study published in Science Advances . The technology was developed by Professor Laura Ballerini’s team at SISSA in Trieste in collaboration with the Universities of Chicago and Cambridge.

When activated with infrared light, nanoscale photodiodes send electrical messages to the nerve cells to which they bind, regulating its function. The effects of the stimulation can then be extended and amplified to the surrounding network of neurons through their synaptic contacts. Working like real electrodes but with a non-invasive and selective approach, these nanotechnologies are useful for basic research, delving into the mechanisms of the nervous system, and developing targeted therapies for neurological diseases.

Nanophotodiodes: Here’s What They Do Principles

“In order to study the function of the nervous system , there is now a great deal of interest in techniques that have to be very precise and non-invasive. Our strategy is moving in exactly this direction. Unlike what has been explored so far, using metal electrodes or a combination of genetic manipulation and optical techniques, optogenetics, We pursued a new, more specific and less invasive approach,” said Professor Ballerini and her collaborators Denis Scaini and Mario Fontanini.

In the study, the SISSA research team used innovative nanophotodiodes developed at the University of Chicago, capable of combining surface film. “The photodiode lights up when illuminated with infrared light,” explain the scientists. “In this way, they can have an electrical effect on the nerve cell, activating it. This is very useful for research purposes because it allows us to see what role a particular neuron is playing in a given process, and because infrared light can penetrate penetrates the tissue and modulates it to move from the outside in an agile and non-aggressive way.”

But how to connect the photodiode to the neuron you want to study? Thanks to an ingenious mechanism developed in collaboration with Ljiljana Fruk’s group at the University of Cambridge: “The photodiode binds to the antibody and, like a courier, hangs it exactly where we want it to be. This is because the antibody is highly specific Sexual recognition structures we know are on the surface of the target neuron.”

New technology with great potential

SISSA staff working on spinal cord explant sections in the laboratory, focusing on the sensory neurons involved in pain pathways: “We realized that our approach was able to selectively stimulate individual cells, allowing us to activate individuals with opposite functionally acting neurons, such as excitatory or inhibitory,” the researchers explained. “By activating excitatory neurons in the dorsal horn of the spinal cord with photodiodes, we witnessed an amplification of pain signals. And vice versa, by acting on inhibitory neurons, the opposite effect was obtained: the amplification of pain signals was turned off.”

Interestingly, research has also shown that acting on just one neuron can have broader effects, affecting entire neurons activity area. “That’s exactly what we’ve verified: By stimulating the target neuron, we can modulate the response of the entire circuit, which is very interesting for a number of reasons,” the researchers said.

“Due to its functionality and efficiency, this technology, which has so far been developed only in vitro, allows us to Defining neurosensory circuits in complex ways, obtaining highly detailed information about the role of individual nerve cells in different mechanisms. This in-depth knowledge will therefore allow the design of increasingly specific treatments at the spinal cord level,” concludes Laura Ballerini.

More information:
Agnes Thalhammer et al., Distributed interface of nanoscale photodiodes enables single-cell 3D spinal explants Neuronal photoactivation and sensory enhancement, Science Advances

(2022). DOI: 10.1126/sciadv.abp9257.
: When the light is a switch: Nanophotodiodes for Studying Neuronal Activity (12 Aug 2022) Retrieved 18 Aug 2022 from

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