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, findings that led to the 2014 Nobel Prize in Medicine. Failure of these networks to function properly, as seen in Alzheimer’s disease and other neurological conditions, results in severe disorientation and memory deficits. Researchers at NERF (VIB-imec-KU Leuven) have now uncovered striking neural activity patterns in a brain area called the retrosplenial cortex that may assist with spatial memory and navigation.
The prime example of spatial information coding is the firing of so called place cells in the hippocampus, a brain area known for its role in navigation and memory formation. Place cells fire when an animal enters a specific place in its environment. At any given location, only a small fraction of place cells is active, leaving the remaining neurons largely silent. This sparse firing pattern maximizes information storage in memory networks, but at the same time minimizes energy demands.
The hippocampus, however, is not the only brain area involved in spatial orientation and learning. The retrosplenial cortex is also highly active during navigation and memory retrieval and connects the hippocampus to the visual cortex and other areas of the brain. Damage to the retrosplenial cortex results in memory deficits and disorientation, and patients with Alzheimer’s disease have reduced activity in their retrosplenial cortex.
To better understand the role of the retrosplenial cortex, Drs. Dun Mao and Steffen Kandler, researchers in the laboratories of Profs. Vincent Bonin and Bruce McNaughton at NERF, measured its activity in mice that moved on a treadmill fitted with tactile stimuli. In this setting they could precisely track the animal’s behavior and location. By combining genetic labeling of cortical neurons and highly sensitive live microscopic techniques, the researchers were able to compare the activity of the neurons in the retrosplenial cortex with those in the hippocampus.
“Previous studies could only record from a few retrosplenial neurons simultaneously. With our cellular imaging technique, we could monitor the activity of hundreds to thousands of neurons simultaneously, which gave us a rich view into the neurons’ activity patterns,” explains prof. Vincent Bonin.
The researchers discovered a new group of cells that fire in smooth sequences as the animals run in the environment. Their activity resembled that of hippocampal place cells in terms of their sparse firing properties; however, the retrosplenial neurons responded differently to sensory inputs.
These results indicate that the retrosplenial cortex carries rich spatial activity, the mechanisms of which may be partially different from that of the hippocampus. They pave the way for a better understanding of how our brain processes spatial information. Prof. Vincent Bonin: “The next step is to investigate directly the relationship between retrosplenial activity and hippocampus as well as its link to visual inputs. It will also be interesting to know how activity in the retrosplenial cortex relates to the development of different neuronal diseases in mouse models.”
The study is an international collaboration between the laboratories of Dr. Vincent Bonin at NERF and Dr. Bruce McNaughton at the University of Lethbridge, Canada. Dr. Bonin is Principal investigator at NERF and VIB since 2011 and Associate Professor at KU Leuven since 2017 (Assistant since 2012). Dr. McNaughton is AHFMR/AIHS Polaris Research Chair at the Canadian Centre for Behavioural Neuroscience at The University of Lethbridge, and Distinguished Professor of Neurobiology and Behavior at UC Irvine. Dr. McNaughton held a Senior Visiting Scientist position at NERF from 2010 to 2013. The work was supported by core grants from imec, VIB and KU Leuven and from the Government of Flanders as well as research awards from FWO, Alberta Innovates: Health Solutions, NSERC, and NSF.
Questions from patients
A breakthrough in research is not the same as a breakthrough in medicine. The realizations of VIB researchers can form the basis of new therapies, but the development path still takes years. This can raise a lot of questions. That is why we ask you to please refer questions in your report or article to the email address that VIB makes available for this purpose: email@example.com. Everyone can submit questions concerning this and other medically-oriented research directly to VIB via this address.
Basic research in life sciences is VIB’s raison d’être. On the one hand, we are pushing the boundaries of what we know about molecular mechanisms and how they rule living organisms such as human beings, animals, plants and microorganisms. On the other, we are creating tangible results for the benefit of society. Based on a close partnership with five Flemish universities – Ghent University, KU Leuven, University of Antwerp, Vrije Universiteit Brussel and Hasselt University – and supported by a solid funding program, VIB unites the expertise of 75 research groups in a single institute. VIB’s technology transfer activities translate research results into new economic ventures which, in time, lead to new products that can be used in medicine, agriculture and other applications. VIB also engages actively in the public debate on biotechnology by developing and disseminating a wide range of science-based information about all aspects of biotechnology. More information: www.vib.be.
KU Leuven (University of Leuven) is a leading European research university dedicated to excellent research, education and service to society. It is a founding member of the League of European Research Universities and has a strong European and international orientation. Its sizeable academic staff conducts basic and applied research in a comprehensive range of disciplines. University Hospitals Leuven, its network of research hospitals, provides high-quality healthcare and develops new therapeutic and diagnostic insights with an emphasis on translational research. The university welcomes more than 57,000 students from over 140 countries.Its doctoral schools organise internationally oriented PhD programmes for over 4,500 doctoral students. More info: www.kuleuven.be/english/
Vincent Bonin (Expert Press and Public Communication VIB)
Mobile: +32 473 78 05 52
Sooike Stoops (Expert Press and Public Communication VIB)
Tel.: +32 9 244 66 11
Mobile: +32 474 289 252