A new McGill University study has found a direct link between age‑related declines in neuron activity in the cerebellum and worsening motor skills, including gait, balance and agility. While it is well known that these abilities diminish with age, this is the first research to pinpoint how changes in Purkinje cells - a key type of cerebellar neuron - drive this decline and translate into measurable changes in behaviour and physical function.
"By demonstrating how the changes that happen to Purkinje cells in age are causally linked to changes in gait, motor co-ordination and balance, our work provides new avenues for therapies that may prevent or delay motor aging," explained Eviatar Fields, the study's lead author and McGill doctoral student in the Integrated Program in Neuroscience. "This provides new hope for extending health span and ultimately improving quality of life and independence in elderly people."
The findings have significant implications for such public health measures as fall prevention. They may also help clarify why similar neural disruptions appear in Alzheimer's disease and other neurodegenerative disorders.
The research was conducted with Professor Alanna Watt's lab in the Department of Biology.
The mind-body connection
Purkinje cells process sensory input and internal signals from the body and send corrective messages that finetune movement. However, unlike other neurons, they can also spontaneously fire electrical signals. To test how aging affects this activity, the researchers examined motor co-ordination in mice ranging from young adults (two months old) to elderly (18 to 24 months old). Older mice performed worse on several co-ordination tasks, including crossing an elevated beam and staying on a rotating rod (Rotarod), mirroring motor decline in humans.
The team then recorded electrical activity from Purkinje cells and found significantly lower firing frequencies in older mice. To determine whether this caused the behavioural decline, they used a genetically targeted tool called a DREADD, a type of designer receptor that increases or decreases neuron excitability when activated.
"When we turned on the DREADD for young mice, which made their Purkinje cells fire at lower rates, mimicking the older Purkinje cells, we found that they jumped off the Rotarod sooner than young mice who did not have the DREADD," Fields explained. The reverse was also true: when the researchers boosted neuron firing in older mice, those mice stayed on the Rotarod longer, suggesting improved motor co-ordination.
"We showed that spontaneous firing rates in older Purkinje cells are reduced, and if we reverse this, we improve co-ordination. This indicates that the change plays a direct role in the age-related decline of motor co-ordination," Fields said.
A second test produced similar results. After being trained to pull a one-metre string for a cereal reward, older mice made more errors than younger ones. But when the researchers increased Purkinje cell firing in the older animals, the older mice made significantly fewer mistakes than they had previously.
Professor Watt, study co-author, noted that ongoing research in this field is necessary to support an aging population.
"Motor co-ordination has been under-explored in the aging field. It's important to study this, because as co-ordination declines, falls become more common, which can have a catastrophic impact on quality of life," she said.
About this study
"Cerebellar Purkinje cell firing reduction contributes to aging-related declining motor coordination in mice," by Eviatar Fields, Alanna J. Watt et al., was published in Proceedings of the National Academy of Sciences.
The research was funded by the Canadian Institutes for Health Research, the Canada First Research Excellence Fund, the Fonds de recherche du Québec, the Natural Sciences and Engineering Research Council of Canada and a Dr. Stephen J. Zalcman Memorial Scholarship.
