Researchuncoversnewinsightintothehippocampus

U OF L’S CCBN, NEUROELECTRONICS RESEARCH FLANDERS IN BELGIUM TEAM UP FOR STUDY

The Canadian Centre for Behavioural Neuroscience at the University of Lethbridge has provided new insight into how the brain learns about the environment and why the hippocampus, a key part of the brain, is very important to this process.

The research collaboration between Dr. Bruce McNaughton’s lab at the CCBN and Dr. Vincent Bonin’s lab at the NeuroElectronics Research Flanders in Belgium, brought the new discovery to light with alternative evidence, compared to the behavioural evidence it previously relied on.

“This is quite a major breakthrough in understanding and supporting a longstanding theory for which there was virtually no neurophysiological evidence, mostly just behavioural evidence and conjecture,” said McNaughton in a news release.

A study in 2017 conducted by Dr. Dun Mao, followed by a graduate student working in the labs of McNaughton and Bonin, was the first to show cells in the cerebral neocortex, specifically the retrosplenial cortex, look very similar to “place cells” in the hippocampus. How an individual learns and navigates involves healthy place cells.

“Navigating and remembering rely on extensive interactions between the hippocampus and the neocortex,” said Mao, now a post-doctoral fellow at Baylor College of Medicine in Houston, Texas. “This study provides the first direct evidence of the role of the hippocampus in sending a continuous, sequential code to the neocortex. I think it will inspire a new direction of research in the field.”

The study, “Hippocampus-dependent emergence of spatial sequence coding in retrosplenial cortex,” has now been published in the Proceeding of the National Academy of Sciences of the United States.

The idea for the study developed from the long-held hippocampal indexing theory. Neuroscientists have proposed the indexing theory to explain how the hippocampus interacts with the cortex. The brain’s cortex has many cells, making a weaker communication between distant regions in the brain. However, each part of the cortex is able to store information in its own domain.

During the current study, Mao damaged very precise locations in the hippocampus in mice so the hippocampus was no longer functional but the cortex remained intact. He then used 2-photon calcium imaging to track the activity of neurons in the cortex as the mice learned about the environment and navigate within it. This allowed him to witness how retrosplenial activity develops and how to determine the exact role of the hippocampus.

“In those mice, we found that there was a loss of this place-cell like activity in the cortex, thereby strongly supporting the conclusion that the cortex gets its spatial code, or its index code, from the hippocampus itself,” said McNaughton.

“Most compelling are the strength and specificity of the effects,” added Bonin. “The effects are stunning. With an intact hippocampus, activity in the retrosplenial cortex is precise and orderly. In the absence of it, it’s a complete mess, as if the animal had never been exposed to the environment. Having such a strong phenomenon to rely on will be helpful in basic studies but also in studies of brain disorders and neurodegeneration.”

The results from the hippocampus study will help pave the way for future studies to determine how general the phenomenon is, and to determine how and if indexing activity helps the cortex retrieve stored information.

McNaughton is looking forward to the future studies as new high-tech tools should be available in the next five years that will allow for a deeper exploration into the brain, as well as techniques that will allow for simultaneous recording of the activity of tens of thousands of brain cells, rather than a few hundred which is currently possible.