Navigation and spatial memory — brain region newly identified to be involved

caroline.zentner — Wed, 16 Aug 2017 17:56:08 +0000

Research conducted in a collaboration between Drs. Dun Mao, a researcher in Dr. Bruce McNaughton’s lab at the Canadian Centre for Behavioural Neuroscience at the ��Ѹ��Դ��߿�Ƭ of Lethbridge, and Steffen Kandler, a researcher in Professor Vincent Bonin’s lab at Neuro-Electronics Research Flanders (NERF) in Belgium, has found neural activity patterns that may assist with spatial memory and navigation.

Their study, Sparse orthogonal population representation of spatial context in the retrosplenial cortex, has been published in Nature Communications.

Dr. Dun Mao, who received his PhD in neuroscience this spring, is now a postdoctoral fellow at Baylor College of Medicine in Houston, Texas.

“Previously, we knew little about how spatial information is encoded in large neuronal populations outside of the hippocampal formation,” says Mao (PhD ’17), who’s now a postdoctoral fellow at Baylor College of Medicine in Houston, Texas. “Now we have revealed that the retrosplenial cortex, which is highly connected with the hippocampus, encodes spatial signals in a way similar to the hippocampus. These results will help us understand how the hippocampus and neocortex interact to support spatial navigation and memory.”

Navigation in mammals, including humans and rodents, depends on specialized neural networks that encode the animal’s location and trajectory in the environment, serving essentially as a GPS (global positioning system). Failure of these networks, as seen in Alzheimer’s disease and other neurological conditions, results in severe disorientation and memory deficits.

When an animal enters a specific place in its environment, ‘place cells’ in the hippocampus, a brain area known for its role in navigation and memory formation, begin firing. At any given location, only a few place cells are active, with the remaining neurons being largely silent. This sparse firing pattern maximizes information storage in memory networks while minimizing energy demands.

In addition to the hippocampus, the retrosplenial cortex is involved in spatial orientation and learning and has dense connections with the hippocampus. To better understand its role, Mao and Kandler measured activity in the retrosplenial cortex in mice as they moved on a treadmill fitted with tactile stimuli. As they precisely tracked the animal’s behaviour and location, they used highly sensitive live microscopic techniques to compare the activity of neurons in the retrosplenial cortex and the hippocampus.

The researchers discovered a new group of cells that fire in smooth sequences as the animals run in the environment. While the activity resembled that of place cells in the hippocampus, the retrosplenial neurons responded differently to sensory inputs.

“We found these two functional cell types in the retrosplenial cortex, one devoted to spatial mapping and the other devoted to visual processing. We are now studying how these two information streams interact in the retrosplenial cortex,” Mao says.

The results show that the retrosplenial cortex carries rich spatial activity, the mechanisms of which may be partially different from that of the hippocampus. While more research is needed to investigate the relationship between retrosplenial activity and the hippocampus, the results pave the way for a better understanding of how the brain processes spatial information.

Dun Mao’s goal is to help people with memory disorders through neuroscience research

caroline.zentner — Wed, 31 May 2017 16:39:19 +0000

As a child, Dun Mao set his sights on becoming a scientist. That dream will become reality on Thursday, June 1 as he receives his doctoral degree in neuroscience during convocation ceremonies.

Originally from China, Mao started on his scientific path by obtaining a bachelor of science in biomedical engineering at Zhejiang ��Ѹ��Դ��߿�Ƭ. He then spent a year as a graduate student at the Buzsaki lab at Rutgers ��Ѹ��Դ��߿�Ƭ in New Jersey learning large-scale electrophysiology before joining the McNaughton lab at the Canadian Centre for Behavioural Neuroscience at the ��Ѹ��Դ��߿�Ƭ of Lethbridge.

“The training environment here in neuroscience is one of the best in Canada and worldwide, especially in behavioural neuroscience and systems neuroscience,” says Mao. “We have several leading neuroscientists and we have a state-of-the-art research setup. We have a vibrant graduate community and all of this makes it a very good environment to do neuroscience research. I feel happy that I chose the U of L. It’s really been an unforgettable experience.”

The skills he learned while studying biomedical engineering have proved valuable in studying neuroscience, a field that increasingly requires multi-disciplinary approaches, including mathematical modelling, programming to analyze data and engineering to build research apparatuses. Mao is interested in the interactions between two regions in the brain: the hippocampus, thought to be the centre of memory, and the neocortex, thought to be involved in sensory perception, cognition, spatial reasoning and language.

Scientists believe the hippocampus is where new memories are formed. During sleep, memories get consolidated in the cortex, so there is communication between the hippocampus and the neocortex for information exchange and long-term storage of the memories. Most people find that various cues can trigger memories; scientists believe this process also depends on the hippocampus.

“I’m working on the retrosplenial cortex, a specific region in the neocortex,” says Mao. “This region is unique in that it has dense connections with the hippocampus. We chose to study this because of this unique position. It receives lots of hippocampal output so to understand the hippocampal-cortical interaction during spatial navigation or memory processing, this is the first neocortical region we would look at.”

For his doctoral work, Mao studied how the retrosplenial cortex functioned in visual processing and spatial navigation. He looked at single neuron activity in the retrosplenial cortex using a two-photon microscope.

“With this microscope, we can look at hundreds to thousands of cells simultaneously. This is important because we really need to look at the activity of lots of cells to understand what this region is doing during behaviour,” Mao says.

Using a mouse model, Mao found that neurons in the retrosplenial cortex behaved much like neurons in the hippocampus, mapping the environment and encoding a lot of visual information.

In collaboration with the Bonin lab at the ��Ѹ��Դ��߿�Ƭ of Leuven in Belgium, this work was recently accepted by the journal Nature Communications and should be published in the next couple of months.

Mao’s studies at the U of L were assisted by an Alberta Innovates: Health Solutions Graduate Studentship and U of L scholarships.

“All of this allowed me to focus on my research, for which I feel very grateful,” he says.

Since defending his PhD thesis in December 2016, he has been finishing follow-up experiments. Mao will leave Lethbridge for Houston, Texas at the end of July to take a position as a post-doctoral fellow at Baylor College of Medicine and continue his research in a primate lab. He hopes to eventually have his own laboratory at a university.

“The problem is that there is a big gap between rodent research and primate-human research,” he says. “We understand a lot about what the hippocampus and cortex are doing but we don’t really know how we can translate that to higher order mammals. I want to bridge this gap and hopefully it can translate into better understanding of the human brain. I hope to study some of the disease models, such as Alzheimer’s disease, which is highly hippocampus-related. Hopefully this basic research in animals will help us understand humans and help us understand neurological diseases.”

When he’s not working or studying, Mao has used his time in Lethbridge to enjoy the great outdoors, including hiking, camping and snowboarding. He also enjoys playing badminton. He’s participated in the Southern Alberta Summer Games, earning a gold medal in men’s doubles and a silver medal in men’s singles.

UNews - retrosplenial cortex

Navigation and spatial memory — brain region newly identified to be involved

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