Dom Alcino and the Age of Discoveries

From: Learning and Memory

When I learned, shortly before speaking with him, that Alcino Silva had received the 2008 Order of Prince Henry award for his contributions to neuroscience, I must admit that I didn’t think much of it.

After all, governments give awards all the time; and the fact that Silva, who grew up in Angola before moving to the United States, had his work recognized by the Portuguese government, hardly struck me as anything particularly noteworthy.

The truth is that I had never heard of the Order of Prince Henry. In fact, I had never heard of Prince Henry.

But it turns out that I was missing something. Because Infante Dom Henrique de Avis, the 15th-century Portuguese king commonly known as “Henry the Navigator”, was one of those rare visionary monarchs who was keenly aware of the possibilities of his era: under his astute administrative leadership, the so-called Age of Discoveries, and the Portuguese Empire, began.

For Alcino, however, the most impressive thing about the Infante Henrique wasn’t so much the founding of an empire, but his farsighted recognition of the powers of human ingenuity and how it could best be harnessed.

Howard Burton in conversation with Alcino Silva, UCLA

“This is a man who established what we now know as an institute at a time when everything was really balkanized. He paid a lot of people to come together and develop navigation, which was very unusual. He gave them large amounts of money and land, and all they had to promise was that they would share everything they knew with each other, which was unheard of.

“Then we went elsewhere — and some of that history is checkered, as you know — but it changed the history of Portugal, and it started this concept that you could develop instruments and share knowledge for the greater good.”

Alcino runs a learning and memory lab at UCLA that is focused on a vast number of topics, from schizophrenia and autism to memory enhancements and aging. One of the founders of the field of molecular and cellular cognition, he and his colleagues focus on understanding the specific molecular mechanisms of neurobiology in the hopes of being able to intervene and repair these mechanisms when they go awry. And even attempting to do such a thing naturally requires a more generalized approach.

“There was a time in neuroscience, twenty or thirty years ago, when knowledge was effectively sealed off into separate compartments: there were molecular neuroscientists, psychologists, and physiologists; and these groups hardly talked to each other.

“Then there were a number of technologies that came into play that allowed these groups to interact and to have something to talk about, to be able to do experiments together. That brought them together. And that is actually the origin of molecular and cellular cognition.

“When I helped form that society, twelve or thirteen years ago, we didn’t have a community of people who worked with molecules and cells and behaviour. But we really needed that kind of community, because it was different than just working in any one of these areas. There were special questions, special needs, special approaches that we had. Our papers looked different. And that’s why we formed that society.

“Nowadays, a great part of the work in neuroscience is work that connects different areas, from molecules all the way to behaviour. But this is a relatively recent change in neuroscience. For most of its history, neuroscience was really separated into different fields.”

Suddenly it is no longer about some award — it’s hard to stop oneself from contrasting this dynamic UCLA neuroscientist with Henry the Navigator himself.

Indeed, the fact that he is keenly engaged in the pursuit of charting the current scientific landscape so as to develop, as he calls it, a “Google Map” for neuroscience, only makes the comparisons between Alcino and his 15th-century compatriot all the more striking. Perhaps, one might think, there is a Portuguese gene for cartography.

But what, specifically, have we learned from all of this restructuring? What’s been discovered?

“We have recently amassed enough evidence to now appreciate that, during learning, we change the synaptic weights — how neurons communicate with each other. These changes in synaptic weights are orchestrated by hundreds of molecules, and these molecules regulate these changes in cell-cell communication in the brain, which, in turn, regulates learning and memory. Molecules that trigger these changes are involved in learning, molecules that maintain these changes are involved in memory.”

The experiments speak for themselves. In Alcino’s lab alone, which works with mice, specific memories have not simply been localized, they have been precisely manipulated.

“In one of our experiments, we have given the animals two memories: first, that a salty substance was not so good because it made them slightly sick, and the second, that there was a tone that was to be avoided because when they heard that tone, they got a buzz, a slight shock.

“What we did then was to change the physiology of the brain in such a way that we determined where one of these two memories went to in the brain, but not the other. We let the other just go into the brain normally.

“And what we were able to do was to get rid of one memory, but not the other. We can manipulate memories in animals by selectively inactivating one memory and not the other. Then we let the animal recover and that memory comes back again. We can literally turn the switch on and off on memories now with the special tools that we have designed.

If you’re finding this all too much like science fiction, and not a little unnerving, it’s time to unveil some unequivocally positive news from the neuroscientific front lines.

Alcino and his colleagues have explicitly and repeatedly demonstrated that it is possible to reverse the cognitive deficits, the learning and memory deficits, of an animal model of something called neurofibromatosis type one, or NF1 for short, a genetic disorder that is responsible, in 30–40% of patients, for a wide range of learning difficulties involving memory, spatial navigation, attention and motor coordination.

That Alcino and his colleagues have been able to coherently construct and analyze mouse models of this condition is impressive enough. That they’ve found some pharmacological treatments that allow the animals to cope better is inspiring. But actually reversing cognitive deficits through drug treatments? That was truly revolutionary.

Because until recently, the common understanding was that cognitive deficits resulting from developmental disorders were simply irreversible: that once a brain had been damaged in the development process towards adulthood, there was no possibility of making any fundamental repairs.

“These results meant that adult animals that were unable to learn very well, that had problems with spatial navigation and interaction with their environments compared to other animals, could have their learning deficits reversed when we addressed the biochemistry that was affected with a specific drug.

“But the results also demonstrated something that we should have known already: that there’s a tremendous amount of flexibility and plasticity in the human brain, and we systematically underestimate the brain’s resourcefulness at recovering and repairing itself.

“This has been one of the really important things that we found — something with the greatest potential for human impact — it opened the door to the possibility of treating literally hundreds of millions of people worldwide with problems that we never thought we would ever have even a chance of touching.

“I’m convinced that our children, certainly the children of our children, will have a very different relationship with these types of disorders than we have with them today. Think about the time before antibiotics, how the world was: a simple cut could kill you. Now, we don’t even think about it, we cut ourselves, sometimes severely and we just wash it, treat it, take antibiotics, and most of us easily move on.

“Just imagine a time when for parents of a child with neurofibromatosis, with autism, with schizophrenia, with any of these horrible, horrible disorders, it will be like a cut — something you need to address, something you need to treat, but hardly a life-changing condition like it is now.”

Just imagine. Truly, a sparkling new land to steer towards.

Howard Burton, howard@ideas-on-film.com

This is the introduction written by Howard Burton of the book called Learning and Memory. This thought-provoking book is based on an in-depth, filmed conversation between Howard Burton and Alcino Silva, Distinguished Professor of Neurobiology, Psychiatry and Psychology at the David Geffen School of Medicine and Director of the Integrated Center for Learning and Memory at UCLA.

The book is broken into chapters and includes questions for discussion at the end of each chapter. Visit the page for Alcino Silva: https://ideas-on-film.com/alcino-silva/ and watch a clip here: https://youtu.be/Uz0HldzwPsM.

This book is also available as part of the 5-part Ideas Roadshow Collection called Conversations About Biology, also featuring Nick Lane, Frans de Waal, Mattew Walker and Stephen Scherer.

Visit our website for further details:

https://ideas-on-film.com/

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