an ultrasound approach allowed mice to perceive a flash of light

2023-06-23 06:00:08
WORLD INFOGRAPHIC

After optogenetics, sonogenetics. In the first case, a neuron is forced to manufacture a photosensitive protein by introducing a gene delivering the instructions for this; then this neuron is activated or inhibited by illuminating it with a laser of specific wavelength. The method is valuable for studying memory, fear, sensory perceptions…

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“But the light does not penetrate very deeply into the brain, unlike ultrasound”, says Mickael Tanter, of the Physics Institute for Medicine (ESPCI-PSL-Inserm-CNRS). In the cerebral tissue, the light does not cross more than 1 millimeter, an insufficient depth to reach the intermediate layers of the visual cortex, under the meningeal barrier.

Hence the idea, to treat certain visual impairments, of replacing the protein sensitive to light with a protein sensitive to ultrasound. This is therefore the principle of sonogenetics, of which the feasibility has been established in mice by the teams of Mickael Tanter and Serge Picaud, director of the Institut de la vision, in Paris.

A channel present in bacteria

There is, in nature, a protein sensitive to ultrasound: a mechanosensitive channel, called MscL, which equips many bacteria. Through this channel, they can “feel” the pressures around them and adapt to them. In the event of a change in the chemical composition of the medium in which they live, they can expel, through this channel, compounds present in their cytoplasm, which thus prevents them from bursting.

First, the researchers injected into the rodent’s visual cortex, through a window cut in its cranial box, an adenoviral vector – rendered harmless – containing the MscL mechanosensor gene. The neurons of the visual cortex incorporated this gene and made this channel, which inserted into their membrane.

Then the authors fixed a high frequency (10 to 15 megahertz) ultrasound generator implant in the animal’s cranium. By triggering the sending of ultrasound, they activated the neurons of the visual cortex.

As a result, the mouse perceived a luminous flash… which did not exist. But how do you know? The researchers first taught the animal to drink water as soon as it discerned a light signal. Then they stimulated the animal’s visual cortex with these ultrasounds: they then observed the same behavioral reflex, but only when the neurons of the visual cortex produced the mechanosensitive channel.

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