Researcher Hideto Takahashi decrypts signals from neurons

Hideto Takahashi
Hideto Takahashi

A discovery by Hideto Takahashi and his team paves the way for a better understanding of the mechanisms of neuropsychiatric disorders.

Did you know? Your body is made up of a hundred billion nerve cells that, like small computers, receive, process and deliver crucial information to your body. These machines are your neurons. They form the very foundation of your nervous system. It is through them that your brain converts the data transmitted by your retina into images and that your mood adapts to the situations you are living.

Hideto Takahashi, a researcher at the Montreal Clinical Research Institute (IRCM) and a Professor at the Faculty of Medicine at Université de Montréal, is like a computer scientist of neurons. By studying the signals transmitted by these “biological processors”, he and his team have discovered a gene that could be associated with certain neuropsychiatric disorders, such as schizophrenia. These results were recently published in Nature Communications.

Neurons and cat videos: a similar struggle

Neurons are distinguished by their elongated form; their length may vary from one millimeter to more than one meter. A real blabbermouth, the neuron speaks constantly with his fellow neurons.

Hideto Takahashi is particularly interested in the tips of these cells, which allow them to communicate. It is indeed thanks to these junction points, called synapses, that chemical signals make their way from neuron to neuron, like a cat video that would spread on the Facebook walls of your friends.

Synapses can both amplify the signal that will be transmitted to the next neuron (excite) and reduce or even suppress it (inhibit). Although these two states may appear to be in competition, they are chosen depending on the circumstances: “It’s all about balance,” says Dr. Takahashi, who is also director of the Research Unit for Plastic Synaptic Development and Plasticity at IRCM. Excited and inhibited synapses are essential to the functioning of our organism. They make sure the information flows in the right places at the right time. ”

When the delicate balance of these signals is disrupted, the situation can reverberate in our brain. Studies show, among other things, that abnormally excited neurons can be associated with neuropsychiatric disorders.

But what influences these different types of signals? Scientists are looking for the answer in our genes. So far, 70 to 80% of the genes found are “exciters”. The other genes studied have a “hybrid” function:  they activate certain receptors of the synapse, but they inhibit others at the same time. However, exclusively inhibitory genes have been rather rare so far, even though there is a large variety of inhibited synapses in the brain. This observation intrigued Dr. Takahashi.

A selective gene

By screening the potential genes responsible for these signals in the mouse, the IRCM group identified an exclusively inhibitory gene that differed from the mass: IgSF21. The team later showed that IgSF21 binds to a protein on the surface of the synapse, neurexin2α. This connection allowed an inhibitory neurotransmitter (GABA) to circulate.

“We were surprised by these observations. Neurexin exists in six forms; neurexin2α is one of them. Normally, genes can interact simultaneously with many forms of neurexin, says Dr. Takahashi. This feature illustrates that IgSF21 is a highly selective gene. This could explain why he has a strictly inhibiting behavior. ”

Dr. Takahashi’s group also found that the presence of IgSF21 is essential for the development of inhibitory synapses in mice. “In mice that did not have the IgSF21 gene, behavior like that of neuropsychiatric disorders associated with a lower level of inhibitors, such as schizophrenia, was observed. It makes sense: Without IgSF21, it’s impossible for neurexin2α to inhibit the signal, “says Dr. Takahashi. These results corroborate those in previous studies that revealed a link between a neurexin mutation and schizophrenia.

What is the next step for Dr. Takahashi? Searching for the human cousins ​​of IgSF21 and neurexine2α, then determining if there are possible mutations of these two genes which would prevent their inhibitory effect on the neurons of the people suffering from neuropsychiatric disorders. In this case, one could try to design a way to “reprogram” the interaction of IgSF21 and neurexin2α to balance signals between synapses. Certainly, our computer scientist of neurons still has many beautiful decryption challenges to tackle!

Original Research Article:

Tanabe Y, Naito Y, Vasuta C, Lee AK, Soumounou Y, Linhoff MW, Takahashi H. IgSF21 promotes differentiation of inhibitory synapses via binding to neurexin2α. Nat Commun. 2017 Sep 1;8(1):408. doi: 10.1038/s41467-017-00333-w.

Source of text: Université de Montréal – Nouvelles : Le chercheur Hideto Takahashi décrypte les signaux des neurones

Translation : CAN-ACN