A team of researchers at the University of Alberta is working to determine the role of a little-understood region of the brain in controlling how mammals learn and make memories, with the goal of one day finding new treatments for neurological disorders such as dementia.
Jesse Jackson, an assistant professor of physiology and Canada Research Chair in Neural Circuits has been awarded a $940,950 grant over the next five years by the Canadian Institutes of Health Research to carry out the research in his lab.
The claustrum is a region deep in the brain that is connected to and communicates with dozens of other parts of the brain. Jackson and his lab recently developed new techniques to study this region’s activity in mice. The claustrum has been hard to image with traditional brain-scanning tools such as functional MRI because of its sheet-like structure and its location deep within the cerebral cortex. Researchers know that the claustrum does not function properly in people with memory-related disorders such as dementia.
The Jackson laboratory team has identified that the claustrum is predominantly active during slow-wave sleep, the deepest sleep that occurs in the first hour of slumber for mammals. It’s already known that memory consolidation — which is necessary for learning — occurs during this time. Memories are encoded based on waking experiences in one region of the brain, the hippocampus, and then transferred to another region, the cortex, for long-term storage.
Jackson’s working hypothesis is that neural activity in the claustrum is key to this memory transfer process during deep sleep.
“It’s very well known that you need sleep to remember, and if you don’t sleep well, you don’t feel good, you’re irritated, and you’ll have trouble performing hard tasks,” says Jackson, who is a member of the Neuroscience and Mental Health Institute and the Women and Children's Health Research Institute. “We know that during this slow-wave sleep, the hippocampus is active and memory consolidation is taking place. We want to understand how the claustrum is aiding this communication.”
A potential treatment target in the future
While Jackson’s team works with mice to understand the function of the claustrum, the ultimate goal would be to develop ways to stimulate the claustrum as a potential treatment for human memory disorders in the future.
All mammals have this thin claustrum region in their brains. Situated beneath the much larger cortex, the claustrum is densely connected to other parts of the brain through neural pathways. Changes to the claustrum have been identified in neurological diseases like epilepsy, stroke, schizophrenia and Parkinson’s disease.
Jackson’s method of tracking claustrum activity is non-invasive. He uses a high-resolution microscope to take snapshots of a fluorescent calcium tracer that only lights up when the claustrum neurons are communicating, providing a readout of neural activity within one micron (one-millionth of a metre) in real time.
For this study, the team will monitor claustrum activity during sleep to determine the pathways of communication between the hippocampus, claustrum and cortex in healthy memory-building. Then they will test how activating or suppressing claustrum activity during sleep modifies memory-building in both adult and aged mice.
“It’s known that people get less deep sleep as we age, and sleep fragmentation has a deleterious effect on memory,” Jackson says. “We are finding that claustrum stimulation mimics the normal pattern of the brain during sleep, and one hour of stimulation in that first phase of deep sleep helps mice remember things that they were exposed to the day before.”
Jackson has five other projects looking at the anatomy, physiology, development, function and dysfunction of the claustrum in disease states. He frequently collaborates with Romain Goutagny’s team at the University of Strasbourg and with others. For example, he worked with Anna Taylor, associate professor of pharmacology, Alberta Cancer Foundation Chair in Palliative Care and Canada Research Chair in Pain and Addiction, to identify how claustrum dysfunction contributes to chronic pain. The pair hope to identify a drug that activates claustrum cells as a potential chronic pain treatment in the years ahead.
U of A projects receive more than $12M from CIHR
Jackson is just one of the University of Alberta researchers who were awarded a total of more than $12 million by the Canadian Institutes of Health Research in its most recent round of grant announcements. Twelve U of A projects were fully funded by CIHR:
Todd Alexander, Faculty of Medicine & Dentistry
Leveraging a large cohort of patients with a unique, frequent renal sodium phosphate cotransporter, SLC34A3, pathogenic variation to understand and treat osteoporosis and kidney stones
$967,726
Scott Garrison, Faculty of Medicine & Dentistry, Jeffrey Bakal, Faculty of Medicine & Dentistry, James Silvius (Alberta Health Services)
MinMed: partnering with data custodians to transform pragmatic trials and improve prescribing in older adults
$753,525
Simon Gosgnach, Faculty of Medicine & Dentistry
Investigating functional connectivity within the mammalian locomotor CPG
$810,900
Padma Kaul, Faculty of Medicine & Dentistry
Evaluating community gathered ECGs for survival and adverse event forecasting (the ECG-SAFE Study)
$895,401
Gary Lopaschuk, Faculty of Medicine & Dentistry
Cardiac energy metabolism in HFrEF and HFpEF
$1,071,000
Sherif Mahmoud, Faculty of Pharmacy & Pharmaceutical Sciences
Nimodipine systemic exposure and outcomes following aneurysmal subarachnoid hemorrhage: A prospective multicentre observational study (ASH-II Study)
$722,926
David Marchant, Faculty of Medicine & Dentistry
Respiratory syncytial virus immune avoidance, entry receptors and how they affect human parainfluenza coinfections
$711,450
Richard Oster, Faculty of Agricultural, Food and Nutritional Sciences / Faculty of Medicine & Dentistry
Understanding the effectiveness of the Métis Settlements Primary Care Initiative from a community-based perspective
$531,675
Gavin Oudit, Faculty of Medicine & Dentistry
Cardiovascular disease in post-COVID condition: Taurine and ACE2 probiotics as potential therapies
$1,002,150
Thomas Simmen, Faculty of Medicine & Dentistry
The TMX2 redox web as a paradigm for endoplasmic reticulum-mitochondria contact site (ERMCS) pathologies
$971,550
Richard Thompson, Faculty of Medicine & Dentistry, Ian Paterson (University of Ottawa Heart Institute)
Imaging of long-term tissue damage from COVID-19 and cardiometabolic disease
$887,400
Anastassia Voronova, Faculty of Medicine & Dentistry
Role of MS genetic variants in neurodevelopment
$1,143,676
U of A projects funded through Priority Announcement Awards
Margaret Davenport, Faculty of Kinesiology, Sport, and Recreation
International practice and policy for pregnant and postpartum athletes
$100,000
Katharine Magor, Faculty of Science
H5N1 influenza interferes in RIG-I signalling in avian and human hosts
$100,000
Hannah O’Rourke, Faculty of Nursing
Connecting today to combat social isolation and loneliness: An evaluation of a remote visiting program for care home residents living with dementia
$300,000
Carrie Ye, Faculty of Medicine & Dentistry
ChatRheum: Developing and evaluating a source-verified large language model to answer rheumatology patients’ questions
$100,000
U of A-led projects funded through CIHR Team Grants
Anne Hicks, Faculty of Medicine & Dentistry
Team Grants in Lung Health: Interventions to address exposure and health outcomes linked with air pollution and climate change — an interdisciplinary team approach
$1,799,331
Stephanie Montesanti, School of Public Health, Lyndsay Crowshoe (University of Calgary), Val Austen Wiebe (Alberta Health Services), Esther Tailfeathers (Blood Reserve)
Team Grants in Strengthening the Health Workforce for System Transformation: Implementation of a novel Indigenous hub-and-spoke model of care in primary care networks (PCNs) in Alberta
$749,162
Patricia Gongal, Faculty of Medicine & Dentistry, Lori West, Faculty of Medicine & Dentistry, Megan Levings (University of British Columbia)
Intervention Trial in Inflammation Chronic Conditions - Knowledge Mobilization Hub: A Knowledge Mobilization Hub for the Canadian Inflammation Research Community
$580,000