The Holy Grail of neurosciences could be found in a circuit of 30 neurons located in the stomach of a crustacean. Biologist Eve Marder explains to us how it is possible that this mini-brain provides invaluable information about the functioning of our brains.
Imagine that you have built an airplane and now you have to change each and every one of its parts in mid-flight. It is not possible to take the aircraft to the hangar, or turn it off, much less leave it out of service for a few months. Well, that is what happens to our brain. Every minute of every day something is exchanged or replaced at the molecular level, without the organ stopping working, losing a single memory -in the case of a normal brain- or forgetting something learned in childhood. In his laboratory at Brandeis University in Waltham, Massachusetts, theneuroscientific Eve Marderwants to find out how it is possible. He has been mulling over this question for 40 years, one of the most complex in biology, implicated in the development of a good number of mental illnesses.
The subjects of his study arelobster and crab larvae, but what Marder is interested in are specificallythe nerves that line their stomachs. These clusters of cells produce rhythmic discharges that can be collected with electrodes and sent to a computer. Although it is a circuit of only 30 giant neurons, it is very important. In fact, it controls the stomach muscles of these crustaceans, allowing them to digest their food.
“We want to understand how the power generated by a neural circuit depends on the properties of individual cells and the interactions of theirsynapse-the connections between neurons? “, says Marder slowly. And adds:”We use the stomach of lobsters and crabs because it is a small system where we can manipulate the nerve signal cleanly.. The experiments, which are very rigorous, allow us to answer fundamental problems related to the way in which we understand all nervous systems. The stomach of a lobster is not like that of a person. It looks more like a mouth full of neural tissues. Yeach neuron is quite large, which helps us even more “
Every neuron is thoroughly examined
The guts of these crustaceans have become the best studied model of a central pattern generator, that is, a group of neurons that control a repetitive function, such as breathing or chewing. “We have known for years how nerve cells are connected in that system, but even if we have a diagram to show us, it is not enough to understand how it works.” The next step was, therefore, to know all the characteristics of each individual neuron, from the different classes of voltage-dependent channels – tunnels drilled in the cell membrane that control the transit of calcium, sodium and other ions – that are in each of these cells to the strength of their synapses.
“But even then we did not quite find the crux of the matter, since there are between 25 and surely up to 50 presentneuromoduladores -substances that function as a neurotransmitter, but that reach the extracellular space-. Each of them acts on a subgroup of neurons, so we have to study how the same set of nerve cells can produce a variety of different signals under different conditions. And these, in addition, change due to some environmental factors, such as our hormones or what we eat, “explains this expert.
At first, Marder’s hypotheses caused a strong controversy among neurophysiologists. His proposal was that neural circuits are not fixed, but can be altered by neuromodulators. The researcher highlights the differences that exist between these substances and neurotransmitters: “A neurotransmitter is a compound that binds to the receptor of a neuron to open and close its ion channels. This happens quickly. The neuromodulator, for its part, fixes to the cell’s receptor and alters the biochemical properties of that neuron in a different way. Neuromodulators produce lasting – and slower – changes in the way neurons respond to neurotransmitters that allow the cell to communicate with its neighbors. ” . These substances alter the intrinsic excitability of the nerve cell, modify the amount of neurotransmitter that is released each time it starts to function and even the way it works. In addition, they are fundamental in brain homeostasis, the phenomenon that Marder’s laboratory has been studying for 15 years and that is summarized in one question:What rules allow neurons to do their job well?
Brains ready to process everything
“The brain faces a very complicated challenge: it has to incorporate new information, respond to it and at the same time remain stable. For example, we learn to speak when we are small.We continually feed the brain with new information, but this does not mean that we lose the ability to do other important things.There is the problem. How do we build a stable circuit and maintain its function even when it is altered by experience? “Worse still, all the molecules in each of these neurons continually remake themselves.” Neurons survive for a very long time and preserve all their memories . I, for example, have neurons that are over 60 years old, “says Marder.” But each protein molecule on the receptors on those neurons changes as the nerve cell rebuilds itself. And yet, I neither stop learning nor forget things. In fact, it doesn’t just happen in the brain. The same thing happens in the heart. Your muscle fibers last for years. But what makes it possible for them to work are the molecules, which change without pause and without destroying the integrity of the heart. “The problem has two dimensions. One is to find out how the functional stability of the brain is maintained despite this constant recycling of elements. The other is to knowhow it maintains a stable functioning that allows the learning and development of plasticity. It’s like writing a computer program and starting to change it and pretending that the system doesn’t crash. “Lately we are asking ourselves a third question,” says Marder. “We know thatour brain is different from anyone else’s. But we still do not understand well to what extent they can differ and still continue to function normally. For example, although in all brains a part of the stem controls our breathing, mine is not exactly the same as yours. Well, he somehow manages to allow us both to breathe well. “
As indicated, some neuromodulators, such asdopaminas and theserotonin, are very important in the development of certain ills. This is the case, for example, of schizophrenia or depression. ? There are also several drugs that interact with systems that depend on some of these compounds – which, by the way, have been discovered in the brains of all animals. Therefore, to understand addiction, pain and mental illness, we have to understand these very important processes.?
While she would like to go unnoticed, Eve Marder, whose work was recognized in 2005 with the Ralph W. Gerard Award from the American Neuroscience Society, cannot help being at the forefront of the investigation. His work is raising so many questions that it keeps a legion of scientists from many different fields busy. Many of them are determined to study the same systems that Marder has described, but in flies and mice. She, for her part, remains loyal to her crabs and lobsters. So much so that he doesn’t even eat them anymore. “I feel sorry for them!” Says this seafood lover.
Angela P. Swafford
