The brain is the most incredible physical structure I know
In recent years, much effort in neuroscience has been devoted to creating maps or "connectomes" of the brain circuits of many organisms, in order to understand how the nervous system generates behavior. Experience with small circuits, for which connectivity was established years ago, shows that these maps are total necessary, but not enough on their own, to understand how the brain dynamic is derived from neuron properties and the interactions among them, allowing us to understand how the brain works.
In recent years, neuroscience has undergone a huge transformation. In your opinion, what have been the main changes?
The brain is probably the most incredible physical structure I know. In recent years, we have seen a huge boom of new technology that has allowed us to ask new questions and carry out experiments we couldn’t even imagine just a decade ago. Techniques like optogenetics, MRI (magnetic resonance imaging) and PET (positron emission tomography) scanners, which can improve clinical research by showing us brain activity, are allowing scientists to study, for example, how the brain produces consciousness and the origin of many mental disorders, one of the main health problems facing us today.
The title of this event organized by B·Debate is How Mind Emerges from Brain. What do and don’t we know about this topic?
The mind is the part of the brain we understand least. We know that the combination of skills and experiences that we call the mind comes from the brain; so studying the brain can provide important information on the mind. But we have just begun to delve deeper into the mind-boggling complexity of the human brain.
Your laboratory is carrying out groundbreaking work on studying brain circuits. Could you give us a quick overview of the main findings of your research?
For years my laboratory has been involved in various aspects of how the brain is restructured as we age, when we learn, when we interact with our surroundings. We have studied a small circuit of just 30 neurons in lobster larvae. We have represented how each and every nerve cell is connected to this system but this drawing isn’t enough to understand the global overview of how the nervous system works and, so, we studied the characteristics of each neuron in the group and this research led us to work on an extremely important aspect: neuromodulation. This is a process that explains how the same group of nerve cells, a circuit, can produce a variety of different signals under different conditions. We discovered that this ability is due to the existence of between 20 and 40 neuromodulators, chemical substances that act on specific neurons and modify their biochemical properties and how they communicate with neighboring cells. This makes the brain circuits modify their behavior; making them dynamic and not static systems.
In the past 20 years we have simulated millions of possible combinations. Only 1-2% of them lead to the dynamics we observe in nature but, nevertheless, this means thousands of combinations that lead to the same behavior.
These studies led us to another highly interesting concept: cerebral homeostasis. Neurons are cells that divide very, very, very slowly in a person’s adult life. Inside our bodies, depending on our age, there may be nerve cells from 20, 30, 40 or even 60 years ago! How does the brain maintain its identity? How does each neuron maintain its identity if they are constantly submitted to changes provoked by neuromodulator substances? We’ve proposed various models that explain how cerebral homeostasis is responsible for this.
Now we are working on variability among animals, which is very important to understand the variations among the brains of healthy human beings. What we have found is that although crab circuits work in a very similar way, their underlying structures are very different and can respond in a different way to certain types of pharmacological agents. This tells us that it is possible for humans to have different responses to medications and to the environment for the same reason.
Your research has shown that the brain is highly flexible on a very basic level…
We are constantly feeding the brain new information. When we learn something new, we don’t forget what we had learned previously, nor do we lose the ability to do other things. This is a challenge for the brain. How does it do it? It’s thanks to this plasticity, but we don’t know the exact mechanism.
But also, each person’s brain is unique. Mine isn’t identical to yours but thanks to the brain’s plasticity, they both allow us to breathe. To what extent can two brains differ and continue to function normally? These are highly complex biological questions that we don’t yet have answers to.
Is that why plasticity has become a hot topic in neuroscience?
Yes, that is why and because we’ve always been fascinated by how we learn, how our brain changes as we age, how our surroundings influence our brain. It’s totally natural and fundamental to try to understand how the brain helps us survive and triumph in the world.
What information does the study of a circuit made up of a small number of neurons give us on other larger, more complex circuits, like in the human brain?
The system we are working on is made up of 30 giant neurons. That allows us to do very rigorous experiments and to draw conclusions that would be more difficult in larger, more complex systems. Logically, a group of neurons in a lobster doesn’t have anything to do with the human nervous system, but anything we discover in a small system is applicable to other larger ones.
What implications does your research have on other fields? Could it help us develop new therapeutic strategies to treat human neurological diseases?
Today we know that some neuromodulators, like dopamine and serotonin, are extremely important in the development of certain diseases like schizophrenia and depression. There are also various drugs that interact with systems that depend on one of these compounds. In order to understand certain mental diseases and be able to treat them, we must first know what these circuits look like and how to modify them.
Various research projects are working to create virtual studies that simulate the human brain. The most famous is the Human Connectome Project. Do you think we’ll ever be able to reproduce the human brain with a computer?
Thanks to the technological breakthroughs, it takes just days to map a neuron. We can build computer models of many parts of the brain and capture some of their characteristics. But we don’t yet have detailed knowledge of the connections among neurons and without that we can't make a precise model of the human brain. The anatomic and functional work to understand the connectome is absolutely key before we can even think about developing a functional model of our brain. I'm not sure it makes much sense to build a model of the whole brain, because it would be so complicated that it would be difficult to draw conclusions. Models are very, very useful when they isolate simple principles, as this allows us to understand them.
In your point of view, what are the main challenges facing neuroscience in the future?
Neuroscientists are facing a huge problem: human neurological and psychiatric diseases. They are so complex and devastating that we want to find answers quickly. But although some answers seem temptingly close, we need much, much, much more basic research to truly understand what is happening. And we won’t get these answers in just a few years: some of them will require one, two or three decades of work…