Team sees collaboration as ‘way forward’

It may seem odd when Schulich School of Medicine & Dentistry professors Lisa Saksida and Tim Bussey talk about rewarding their mice with strawberry milkshakes for using an iPad properly. Yet, this unique approach to research may lead to improved therapies for degenerative diseases, such as Alzheimer’s, Parkinson’s and Huntington’s.

The husband-and-wife research team recently brought their wide array of knowledge and expertise from their Translational Cognitive Neuroscience Lab at the University of Cambridge to their new home at Western.

Bussey and Saksida have both been appointed as professors in Schulich’s Department of Physiology and Pharmacology. Also serving as core members of Western’s Brain and Mind Institute, they will continue to advance their unique touch-screen systems and any other future software designs at the Robarts Research Institute and its Centre for Functional and Metabolic Mapping.

“The recruitment of the research team of Drs. Lisa Saksida and Tim Bussey to Schulich is an important development in the advancement of the school’s highly successful research enterprise,” said Schulich Dean Michael Strong. “Joining us from Cambridge University in the U.K., they will be continuing their work in creating experimental paradigms which may provide meaningful and translatable data about effective therapies for neurological and psychiatric conditions including schizophrenia and Alzheimer’s disease.”

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The driving force behind their research is simple in concept, but difficult in execution – delve deep into the brain’s inner workings and see how thoughts are organized. What are the mechanisms behind thought? What is happening when the organization breaks down?

“The brain is a huge mystery; it’s an extremely complex system and, at this point, we really don’t understand much about it. That adds additional excitement for us because there is so much out there to be discovered about how the brain works,” said Saksida, an artificial intelligence expert who completed her undergraduate studies in Psychology at Western before eventually earning her PhD in Robotics and Neural Basis of Cognition at Carnegie Mellon University. “Most of the diseases our society is facing at the moment – because our population is increasing in age – are diseases of the brain. We’re at a critical point now where it’s absolutely essential we understand the brain better to work on diseases.”

Bussey, a Western Research Chair, agreed. “We’re interested in cognition – learning, memory, attention, problem-solving. We’re interested in how the brain does it, how it’s organized in the brain and what processes underlie these functions. We’re also interested in what goes wrong with cognition in neuropsychiatric and neurodegenerative diseases like Alzheimer’s, schizophrenia and Huntington’s. We’re interested in knowing how things work, because if we don’t understand how the brain works, we can’t fix it when something goes wrong with it. The knowledge flows in both directions – you learn how the healthy brain works from studying what it looks like when the brain is broken, in certain ways.”

The research team is interested in improving ‘translation’ – moving research findings from the preclinical lab to clinical research to developing therapies based on them. That link has been “problematic” in neuroscience, Bussey said, in part because of the methods and approaches used in preclinical research cognition are different from those used in the clinic.

“One thing we’re trying to do is make them more similar, to bridge the translational divide,” he continued.

For example, most human patients, when tested for their learning and memory skills, are tested using computerized tasks similar to video games. Yet, when testing a mouse model, that test is more like a maze. The two simply don’t match up.

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Saksida and Bussey have developed a device that allows them to test mice models using the same and, in many cases, identical tasks to the ones humans are tested on.

The mice have access to a touch screen and interact by touching their nose on different images, testing their learning and memory. They are rewarded with a strawberry milkshake for making the correct choice. If they don’t make the correct choice, the lights in the maze go out.

“A lot of tests that mice are good at involve navigating, finding where something is in the environment,” Bussey said. “Some (researchers) have taken the opposite approach in using virtual-reality navigation in humans – that’s a great approach. Other people emphasize what is called ‘ecological approaches,’ where you try and capitalize, in the animal, on what they do naturally, which is different from our approach because mice don’t naturally play with iPads. There is room for all of these approaches. But we do what we do and so far it’s having some success.”

Saksida added emerging technologies, such as imaging, are important in getting a better understanding of the brain.

“The technology is crucial. We are at a very exciting point right now in the evolution of brain science where we are developing all sort of technologies that are helping us understand the brain better,” she said. “We are developing technologies that are allowing us to manipulate the brain in ways that will help us understand it more deeply, at the cellular and molecular level, and that is essential.

“There are so many different levels of analysis. Someone in the lab might be working at the molecular level; somebody might be working at the psychological level. It’s very difficult to be an expert at both of those levels, so we need people to work together and bring in their own individual expertise, that way we’ll be able to solve this complex problem, which is the brain.”

And collaboration is something the two will undoubtedly be a part of. When they visited Western this past summer, they immediately saw the potential to advance their research.

“I was blown away with how the university is invested in cognitive neuroscience. Every person we talked with, we had an idea for collaboration,” Saksida said. “Western has a lot of top-notch molecular-level research, and it also has fantastic human-level research and where we fit in is bridging those two levels. It’s a natural home for us here. Everybody here seems really interested doing the best science they can and working together as a team, instead of sitting in your own individual lab and competing with the people next door, which you do see at a lot of top-level research institutes. But collaboration is the way forward, specifically in neuroscience.”

“You could tell people here are excited about what’s going on,” Bussey echoed. “You can feel the enthusiasm and ambition.”