In a recent study published in Cell Reports Journal, University of Michigan researchers identified a new class of neuron in the area of the brain most involved in spatial orientation. It may be crucial in creating what people think of as their sense of direction.
These cells, called low rheobase neurons, are located in the retrosplenial cortex, which is the area of the brain that aligns a person’s inner compass and spatial orientation.
The researchers conducted their work in the lab of Omar Ahmed, an assistant professor of psychology, neuroscience and biomedical engineering. Ahmed explained the general role the retrosplenial cortex plays in determining where people are spatially and directionally.
“We’ve known for a long time that the retrosplenial cortex is important for encoding our sense of direction, but we really have no idea how it does that. Those who have lost or damaged their retrosplenial cortex will have a really hard time navigating, they have a hard time getting from their office to their home or from point A to point B,” Ahmed said. “So we decided to dive down and try to understand what kind of neurons exist there and how could they do this?”
Ellen Brennan, a Rackham student in the lab whose research investigated retrospinal cortex neurons specifically and identified the low rheobase cells, explained the method she used called “patch clamp.”
“Patch clamp is this technique where you basically have your brain slices in a solution that mimics what our brains are sitting in in our heads right now, and it keeps the cells and the slices alive and happy for about eight to 10 hours, so I can go into the slices with this glass electrode, and I can attach that electrode to one individual neuron at a time,” Brennan said. “I can send electrical signals through my electrode into that neuron, mimicking other neurons giving it signals to see how that neuron would respond.”
Brennan also elaborated on how she went about investigating what were previously unidentified electrical signals and finding common patterns and properties.
“When we started looking at everything we had collected from all the recordings, we noticed that there was a lot of recordings signals that I couldn’t identify, so we had to run all these analyses, measure all their different electrical properties, and really get to know the numbers and the personalities of these cells,” Brennan said. “All those question marks that were in my notebook, were from something — a neuron — that was behaving the same way and all the numbers started adding up, these were one type of neuron that hadn’t been classified yet.”
Low rheobase neurons are unique with regards to their small size and the speed and consistency with which they fire. Brennan said their size and persistence resulted in the affectionate nickname of “the little neuron that could.”
“These neurons do not adapt. So you could hold them for a full second, which is very long in a neuron’s time frame because their action potentials are 0.4 milliseconds, so if you hold them for a whole second that’s a lot of action potentials, and they will fire really fast the entire time without slowing down,” Brennan said.
Ahmed explained how the unique qualities of low rheobase neurons could potentially propel the mechanisms necessary to have a sense of direction.
“They’re uniquely positioned to integrate both hippocampal information about space and polemic information about head direction, both of those pieces of information are coming into these neurons and when you take those two inputs and combine it with their ability to persistently keep firing, you get their ability to act as a spatial compass,” Ahmed said.
LSA freshman Akash Gandhi, an undergraduate researcher in Ahmed’s lab, said he is excited by the idea that there are many discoveries to be made in the field of neuroscience.
“The coolest part is the idea that it’s 2020 and we’re still discovering these new types of neurons in the brain. As I started to learn more and more about different neuron types and how they interact in the brain, I realized how big of a deal finding this neuron was,” Gandhi said. “When we find these new types of neurons, it’s a big deal because it can help us find new ways to tackle diseases.”
Ahmed tied this breakthrough to potential applications with regards to Alzheimer’s disease research, especially given that many Alzheimer’s patients struggle with spatial disorientation.
“Where we’re taking this now is actually to try to understand what happens in Alzheimer’s. A few studies have now consistently shown that (the retrosplenial cortex) is one of the first regions to show dysfunctional activity in people with Alzheimer’s,” Ahmed said. “So, now we want to understand how these particular unique low rheobase neurons change in the brains of Alzheimer’s model mice.”
Reporter Hannah Mackay can be reached at mackayh@umich.edu.