By adjusting the electromagnetic fields in an MRI machine and utilizing a “chemical shift,” a team led by Prof. Assaf Tal was able to track short-term changes in glutamate and GABA minutes after motor learning – a clue to the chemical encoding of learning and memory processes.
When you want to understand what’s going on in the brain, you usually put subjects into a magnetic resonance imaging, or MRI, machine. MRI generates powerful magnetic fields that allow you to measure the hydrogen nuclei in the water molecules of our brain – and thus identify the active areas. Prof. Assaf Tal from the Department of Biomedical Engineering at Tel Aviv University has a slightly different approach.
“By changing the electromagnetic fields inside the MRI,” explains Prof. Tal, “we manage to suppress the radio frequency of the water, and see what’s underneath it. We’re still looking at the hydrogen nuclei, but in other molecules. We’re investigating questions of learning and memory, but unlike researchers who show, for example, structural changes in the motor cortex of musicians, or measure the electrical activity of neurons – we want to show the coding itself, the way neurons talk to each other while learning.”
To do this, Prof. Tal and his colleagues use a physical phenomenon called “chemical shift”: the radio frequency of hydrogen changes according to the electron cloud that surrounds and masks it, so that hydrogen in different molecules transmits different frequencies. In Tel Aviv University’s MRI machine, they are trying to directly see two molecules in the brains of students studying for assignments: glutamate and GABA.
What is the question? Does the brain also encode learning in neurotransmitters?
“Glutamate and GABA are two neurotransmitters,” says Prof. Tal. “Nerve cells have an action potential, which carries information along the length of the axon, from the beginning of the cell to its end. But the end of the axon of one neuron does not touch the cell body of the next neuron. There is a synaptic gap between them, and they communicate chemically with the help of over 60 neurotransmitters that have been identified to date. And the question arises: Why do we need 60 neurotransmitters? We believe that there is a wealth of phenomena that are encoded in this way, because otherwise we could have been content with one or two. Our main thesis is that in order to understand brain activity, we must understand not only the electrophysiological coding of nerve cells, that is, how they carry information, but also the chemical signaling between them – how they communicate this information between them.”
In general, it is the electrical signals in the brain that produce the secretion of neurotransmitters, secretion that has an excitatory or inhibitory effect – excitation or inhibition: it stimulates the next neuron to produce an action potential, or suppresses it. Glutamate is the brain's main excitatory neurotransmitter, and GABA – the main inhibitory one.
To understand brain activity, we must understand not only the electrophysiological coding of nerve cells, that is, how they carry information, but also the chemical signaling between them – how they communicate this information between themselves.
“It’s true, we would have loved to see all 60 neurotransmitters, but we were lucky to see these two,” says Prof. Tal. “We don’t kid ourselves that tomorrow morning we will solve the problem of chemical communication between nerve cells, but we have shown that there are short-term changes in glutamate and GABA shortly after motor learning, literally a few minutes after performing the task. In other words, the immediate encoding is done chemically, and it is a good predictor of long-term encoding of the ability. Moreover, we see that this encoding is differential, that is: the changes in glutamate encoded certain phenomena and the changes in GABA encoded other phenomena. The ability to distinguish between different processes in learning is in itself very interesting, and we aim to demonstrate that aspects of learning – whether in time frames, in types of learning, or in certain areas of the brain – are encoded chemically, and cannot be measured in the conventional ways of imaging science.”
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