A largely ignored area of the brain called the retrosplenial cortex is getting a lot of attention from Omar Ahmed and his lab with significant implications for ongoing research into Alzheimer’s disease.
Ahmed was drawn to the research because almost no one was studying it and he simply followed the anatomy. “If we look at where the important inputs are converging, it is the retrospenial cortex. It integrates spatial information from the hippocampus, visual information from the visual cortex and movement related information from the vestibular and motor parts of the brain altogether. It’s a massive integration hub,” he explains.
It’s one of the first structures to show impaired activity in Alzheimer’s disease and explains why damage to the retrosplenial cortex is so debilitating for people suffering from the condition. Spatial disorientation is a negative result from damage to this area and makes it difficult for someone to navigate even familiar places. “You could remember every street name on the way home, but you’re not going to get there. You can’t take that information, reconcile it with who you are and where you are right now and figure out a path to get there,” he says.
In a 2003 study, 93% of Alzheimer’s patients reported spatial disorientation. When Alzheimer’s patients were in a PET scanner, the retrosplenial cortex was among the brain regions that were underactive. “We think it’s fundamental to understanding why memory and spatial navigation abilities are lost in Alzheimer’s. The goal is understanding what the retrosplenial cortex does well enough so we can come up with strategies down the line to try to repair it or prevent the damage,” says Ahmed.
Ahmed and his team are trying to understand what’s unique about the structure: what makes it able to carry out various functions, what kind of cells exist and what’s the circuitry of the retrosplenial cortex.
His lab discovered new, fast brain rhythms in the retrosplenial cortex, which they named splines because they look like the teeth on the top of a mechanical gear. They’ve also found a new cell type called low rheobase (LR) cells. These cells are small, bundled together and very excitable; differing from all existing cells in the cortex. “We’re trying to understand what they do during behavior. We assume they are important for encoding head direction and head orientation to tell us where we’re going. If you understand the retrosplenial cells and circuits, you can work towards therapies that target them specifically in Alzheimer’s and other diseases,” he says.
Ahmed says he couldn’t do this type of research in any other department and is thankful for the university’s support helping him get started on this front. He points out, “The amount of equipment and space we need to do this work and make sense of these circuits is sizable. We’re putting the retrosplenial cortex on the radar here at UofM, but we ideally need the whole community deciding it’s important and studying it as a collective.”
With six graduate students, one post-doc and two technicians working in the lab, the research is a group effort. The paper “Mechanisms of fast retrosplenial network rhythms” is in the preparation stage after three years of work and lists every single member of the lab as an author. “I’m very happy and proud of all the names on that paper. We can’t do this without multidisciplinary collaboration by all the members of the lab, and since the Psychology department at UofM attracts really top students, it’s a huge win for us when it comes to research,” says Ahmed.
Megha Ghosh and Danny Siu are Psychology graduate students, Shyam Sudhakar is a Psychology postdoc, and Vaughn Hetrick and Izabela Jedrasiak-Cape are Psychology research staff in the lab. They are joined by Neuroscience gradute students Ellen Brennan, Sharena Rice, Tibin John and Alcides Lorenzo. The team learns about successes and setbacks throughout their research, but Ahmed hopes the biggest lesson they learn is that identifying things that don’t look quite right is how everything starts.
“I think in my training for them, I tell them if it doesn’t look right, be excited, not sad. That’s really the start of something special,” he assures.