Solving the Mysteries of the Brain One Neuron at a Time

As an undergraduate, what drew Roberto Galvez to psychology was the challenge of unlocking the mysteries of the brain. His mission as a neuroscience researcher at the Beckman Institute is to make the brain less mysterious by decoding its workings at the most fundamental levels of cells and molecules.

As an undergraduate, what drew Roberto Galvez to psychology was the challenge of unlocking the mysteries of the brain. His mission as a neuroscience researcher at the Beckman Institute is to make the brain less mysterious by decoding its workings at the most fundamental levels of cells and molecules.

“By and large the brain is viewed as this little black box and people don’t understand what’s happening up there,” Galvez said. “If your heart is racing you’ll go to a doctor and they will give you a pill and fix it. All of the other body’s organs we tend to treat as machines. 

“But when we come to the brain, people say ‘I’m having memory issues’ and then just wonder what’s going to happen. Well, maybe your family members will laugh and you’ll feel bad about it and that will be it. But one of the important things to realize is that the brain is not this mysterious black box; we know a lot about it.”

Galvez has been one of those adding to our increasing knowledge of brain science, especially in the cognitive areas of memory and learning, and in particular a brain region called the neocortex. Galvez is interested in the neocortex (which makes up the top layer of the cerebral hemispheres and is critical to higher mental functions) because of the role it plays in storing memories, and because, as he writes on his website, “the process for storage and subsequent retrieval of learned information in the neocortex still eludes us.”

A member of the NeuroTech group, Galvez’s research mission is driven by both the challenge of finding out, and by imparting what he’s learned to others, including fellow scientists and the general public.

“What drew me to this is that we don’t know,” Galvez said. “It’s definitely more of a challenge. But it’s also not just the challenging aspect of it but the fact that we all have memory issues as we get older. So why is that? What’s changed in our brain that is allowing this process that we don’t even understand to work more efficiently at one point in our lives and now it can’t?”

… one of the important things to realize is that the brain is not this mysterious black box; we know a lot about it.
– Roberto Galvez

Last year Galvez chaired Brain Awareness Day at the University of Illinois, which is sponsored by the Neuroscience Program and part of Brain Awareness Week, an international event that integrates research, institutions, organizations, and communities. He sees community outreach efforts like these as essential to communicating knowledge about the brain, to both educate people for healthier living and to get young people interested in the topic.

“In terms of older individuals I think that is a very important thing to convey,” Galvez said. “In terms of younger individuals, I think just exposing them to the fact that, yes this is something that is within your grasp that you can study. It’s not this mysterious black box that is out of reach. It’s something you can learn about and devote a career towards. And there are a lot of questions to be addressed with it.”

Addressing those questions is what motivated Galvez to change his undergraduate path at the University of California-Irvine from veterinary medicine to psychology. It began with a stint in the lab of legendary neuroscience researcher Jim McGaugh.

“When I started working with Jim McGaugh and doing learning and memory research, I loved the literature, the way that we were addressing the questions, and how we were approaching those questions in the laboratory,” Galvez said. “It was just the fact of not knowing and the exploration of trying to figure out what it was that was happening in the brain.

“With other professions you walk in and you know what you are going to do. If you couldn’t figure out a situation you pull a book off the shelf and you look it up. With research we are literally going into virgin territory and we don’t have the answers. We have to formulate the right questions to even get at the answers. That feeling of exploration and not knowing what tomorrow’s going to hold was what really enticed me.”

McGaugh was also was a mentor to one of Beckman’s founding fathers and a legend in neuroscience circles himself, William Greenough.

“I applied here (for graduate school) and Jim McGaugh said ‘OK you need to talk to Bill.’ Once I started reading up on Bill’s work, I was very interested in his acrobat training and the motor cortex and cerebellum exhibiting synaptic changes. It really enticed me, the idea of how the brain actually consolidates information.”

Galvez earned a Ph.D. in Neuroscience at Illinois in 2004 and, after postdoctoral work, became an Assistant Professor in the Department of Psychology in 2009. His research involving how the neocortex retrieves and stories information seeks to, as he writes, characterize how brain plasticity and “the underlying mechanism necessary for inducing the plasticity is altered with age.”  

What I do is study how our brains store information, what’s happening when we’re trying to form a memory.
– Roberto Galvez

“What I do is study how our brains store information, what’s happening when we’re trying to form a memory,” Galvez said. “How is it that our brains are able to consolidate information and how can we then retrieve that information at a later date? Specifically in terms of what regions I study, it is mostly the neocortex, which most people agree is the predominant site for consolidation.”

And there lies another challenge for Galvez.

“Although most people agree it is the site for consolidation, we still don’t have a good idea as to how that process occurs,” he said. “And what’s actually changing in the neocortex when we consolidate information.”

In order to understand that process, Galvez uses rodent models and molecular scale and electrophysiological methods to characterize learning-induced neocortical plasticity.

“We’re looking at neocortical and gene induction, which genes are being activated in the neocortex, not just after we’ve learned something, but while we’re learning to do a particular task,” Galvez said. “And once we’ve learned, how does the activation of various genes fluctuate during that process. And how does modulation of those genes then affect anatomical properties of neurons during different phases of memory.

“Memory isn’t like a light bulb that goes on and they are formed; it’s a gradual process. You have to study the entire gradual process. I think that’s key to understanding learning.”

At the Galvez Lab, the focus is on the primary and secondary neocortex, especially as it relates to acquisition of information and consolidation, which Galvez describes as associations that are formed during task performance.

“We’re looking to see how these two regions orchestrate their efforts during acquisition and consolidation,” he said. “We have reason to believe that they obviously don’t perform the same function – that would be redundant. So which ones are engaged in acquisition of the task, which ones are engaged in consolidation of the task, and how does plasticity in these two regions then lead to us being able to function normally?”

Galvez is currently collaborating with Lisa Stubbs from the School of Molecular and Cellular Biology looking at tissue microarrays and overall gene expression in the neocortex of rodent models during acquisition and consolidation.  

“We’re also looking at, in terms of primary somato-sensory neocortex, the mRNA activation of that particular region during consolidation and acquisition of the association,” Galvez said. “With secondary neocortex, we’re looking to see how plasticity in that area is modulated depending on how well the animal actually acquires the task and how that’s dependent not just on our acquisition but also the age of the subject, which I think is really key towards consolidation.”

Galvez said the work has implications for understanding cognitive aging in humans.

“When information enters the neocortex there are different levels of processing. The information first goes into the primary cortex and there is some processing that happens that is very important, really important for acquiring a task. Then from there information goes to secondary neocortical structures. There has actually been a lot less focus on secondary neocortical structures.

“The idea that we’re formulating is that consolidation is predominately in secondary neocortical structures,” he added. “So as we get older and have more difficulty with consolidation, maybe we are actually seeing a lack of plasticity in secondary neocortex, as opposed to primary.”

Galvez said the research lines he follows are fairly unique in the field of neuroscience.

“There aren’t many people studying the neocortex and learning and memory,” he said. “A lot are studying the hippocampus and I think that’s great. The hippocampus is very important, but in order to understand how our brains consolidate information, we need to know how things are changing in the hippocampus and the neocortex.

“To look at this picture in terms of not just the neocortex or even one area of neocortex, but try to look at how the different areas of the neocortex interact while we’re acquiring and consolidating an association. I don’t know many people that are doing that.”

In other words, the research is a unique challenge – which is just how Galvez likes it.