New Work in Neuroplasticity

For most of the twentieth century, scientists thought that the brain was fixed or “hardwired,” and therefore considered most brain damage incurable. However, there are new discoveries in neuroplasticity, expectations of what can be achieved and reasons to be optimistic.

Courtesy Sri Ravipati

Courtesy Sri Ravipati

Neuroplasticity, or brain plasticity, describes the brain’s ability to reorganize itself by forming neural connections throughout life. One individual on the forefront of neuroplasticity research is Dr. Sunil P. Gandhi, assistant professor of neurobiology and behavior at UCI.

“Indeed, our early life experiences shape much of our behavior throughout life, and I want to know what is the essential mechanism that makes the brain plastic.”

Gandhi was one of three UCI recipients of the prestigious 2013 National Institutes of Health Direction’s New Innovator Awards this year. He was also named one of 15 Searle Scholars, an award that recognizes innovative biomedical and chemistry research.

“What’s so fun about doing basic research is that you struggle for a long time with technical challenges and then one day the storm clouds clear and you get a glimpse of something that is exquisitely beautiful and you carry it around with you for the rest of your life,” Gandhi said.

Gandhi leads a research team at UCI specializing in neuroplasticity. One that focuses on a particular class of cells called inhibitory interneurons, and these cells are responsible for preventing hyper-excitability in the brain.

“But they do so much more than that, as we have come to learn,” said Gandhi. He says that these interneurons shape processing circuits in the brain. Past discoveries showed that when embryonic inhibitory neurons were transplanted into older brains, they could reactivate levels of plasticity that are normally found in a young brain.

“That has got us thinking that these cells have the key instructions within their development which controls when the brain is plastic,” Gandhi said.

His team has demonstrated that when they transplant these cells into the part of the brain responsible for pattern vision, they can reactivate one of the critical periods of visual development. They experimented this hypothesis by putting these cells into relatively young animals and prying open the early period of plasticity a couple of weeks after it normally closes.

Now funded by the grant from NIH, the team is focused on enacting the experiments on adult animals, again in the visual system, to try and bring back the plasticity that is normally restricted in a critical period of early life.

“Our preliminary results indicate that it works in the adult and we are really excited about this,” Gandhi said.

Beyond plasticity, his studies may also shed light on disorders such as autism and schizophrenia.

“I’m just beginning to become engaged in research relating to autism,”  Gandhi said. He views autism as a critical period disorder when the timing of these programmatic periods of plasticity in the brain have gone awry. As a result, individuals don’t quite have the right patterning of circuits, particularly those relating to social cognition and perception.

“We’re interested in better understanding how the development of these inhibitory neurons relates to plasticity to possibly shed light on what may go wrong in the autistic brain,” Gandhi said.

Gandhi speaks passionately about how far neuroplasticity research has progressed. When asked how neurotransmitters such as GABA fit into the research, Gandhi quickly drew a diagram on the board to help explain how inhibitory GABA cells suppress activity. Although the diagram was a simplified version, Gandhi finds the actual wiring astonishing.

“They do so in a beautiful way, I think, and it comes in many forms. People have likened them to the ‘butterflies of the soul’—that they are so varied in their form, that from starting over 100 years ago we have appreciated their anatomical beauty.”

In recent years, scientists have learned a great deal about the physiology of these GABA cells by putting these cells into a part of the nervous system they never would enter normally in development, such as the spinal chord.

“I think that’s remarkable — that these cells can take route in such foreign territory as the spinal cord. It seems as though there is some program that drives these cells that we want to discover,” Gandhi said.

He is now most interested in working out the developmental programing on the level of genes and proteins that allow the cells to mature in strange environments in the adult brain, which would seem to be completely resistant. His goal is to complete the research that will eventually lead researchers to discover how they might reactivate the plasticity of the brain using less invasive biological manipulations than translation.

“Our hope is that we might find some pixie dust that these cells release on the service — or we might find that it’s the very pattern of connections that they impose upon that works the magic.”

When Gandhi is not busy with research and teaching classes, he is immersed in family life and appreciating the great outdoors. Gandhi is married and has two young sons.  He feels thankful that there is a great sense of community among the faculty at UCI.

“I saw the opportunity to be really happy and work in a place where people believe in removing the obstacles to focus on work,” he said.

“We have a strong sense of belonging to this campus and to this community.”

On his desk stands a captivating photograph of Mt. Rainier, an icon of the Washington landscape notorious for harsh weather. Gandhi is seen climbing through the snow with several of his friends, fellow scientists, on what looks like a perfect day.

“It reminds me of the process of doing science,” he said. “We take these slow, prodding steps always trying to minimize risk, but you are aiming for something quite lofty, and you are aiming for something that cumulatively can be high risk. You take all the precautions you can, but what really gets you up there is a whole lot of effort, a willingness to take risks and also having good friends to the go on the journey with. It’s really meaningful to me, under a lot of technical aspects of it, but in the end all that really matters is the raw experience of being exposed to the elements and getting a lofty view of nature.”