A University of Alberta research team will spend the next five years studying the role of poorly understood spinal neurons in posture and standing, with the goal of one day helping people with spinal cord injury to stand again.
The team, led by primary investigator David Bennett, professor in the Faculty of Rehabilitation Medicine, has been awarded $1,392,300 by the Canadian Institutes of Health Research.
This is just one of 23 University of Alberta research projects to receive more than $18 million through CIHR's Fall 2025 Project Grants and Priority Announcements (see the full list below).
The work will build on 10 years of research by the Bennett laboratory on V3 neurons - highly connected spinal neurons that receive messages from the brain and send instructions to the motor neurons that control muscles in the legs and arms.
"V3 neurons are what I call 'orphan neurons' because we didn't really know what they did in comparison to many other neurons that we know are involved in rhythmic walking movements. They sit quietly most of the time, and we didn't have the tools before to study them," explains Bennett.
Thanks to new molecular methods for genetic identification and manipulation of neurons, Bennett's team discovered that V3 neurons initiate and co-ordinate muscle spasms in mice with spinal cord injuries. They found that when V3 neurons were silenced, the spasms stopped.
Next, they realized that V3 neurons were crucial to the mice's ability to stand. They found that if the V3 neurons were silenced early in life, the mice would figure out other ways to stand but would remain awkward and clumsy. If the V3 neurons are silenced later in life, the mice cannot stand up at all. The researchers also found that they can make paralyzed mice stand up by stimulating the V3 neurons.
"Our research indicates the V3 neurons are pretty much essential for basic postural tone for standing, and if we activate them, we can restore standing ability in animals with spinal cord injury and in uninjured animals," Bennett says.
Bennett cautions that the role of V3 neurons has not yet been definitively proven in humans, but V3-like neurons are known to work this way in zebrafish, mice, rats and cats, and it is highly likely that they work the same in primates and humans.
"There's really no doubt these neurons exist in humans. The key question now is how you would activate them after spinal cord injury to restore standing in humans," he says.
He notes that leg spasms are annoying and even painful for humans with spinal cord injuries, because the legs suddenly lock into a straightened position. Bennett suggests this is remnant V3 activity that is mostly turned off after a spinal cord injury because messages from the brain can no longer reach the neurons.
He says V3 neurons are usually very quiet, only activating and staying turned on when an animal is standing or walking.
"On a day-to-day basis, when you do motions like stand up from your chair, that's V3 neurons," Bennett says. "They're so powerful in their action that the nervous system keeps them under wraps most of the time, otherwise we would have uncontrolled spasms."
Bennett, who is a member of the Neuroscience and Mental Health Institute, cautions that while this V3 neuron research is exciting, it will be many years before it can be confirmed or tested in humans. It's been known for years that by stimulating nerves in a core circuit called the "central pattern generator," people with spinal cord injuries can make walking motions with their legs.
"What was always the missing thing, is that you need to stand before you can walk," he says, noting that when V3 neurons are stimulated, it drives up the heart rate and blood flow.
"We think these neurons are kind of like the centre for saying, 'OK, let's get ready. We're going to stand now. We've got to turn on more breathing, more muscle tone.' And it's co-ordinated. It's not just random," says Bennett.
Future research could explore how to harness muscle spasms in people with spinal cord injury, to allow them to stand. The goal might be to develop a collection of nerve stimulation methods that aid in standing, rather than generating spasms. Another approach would be to use viruses to infiltrate the neurons and use them to control their action.
The Bennett lab is also just completing another grant that looked at using V3 neurons to improve sensory perception following spinal cord injury. That work is expected to be published within the year.
"You can imagine that with spinal cord injury, you're not only losing sensory input to the brain and your sense of limb movement, which you need to make proper movements. You're also losing control over transmission to the brain of those sensory inputs," he explains. "What we found is that activating V3 neurons and other sensory pathways can improve sensory perception after spinal cord injury."
For now, he is focused on the new CIHR-funded project.
"My goal over the next five years is to definitively prove that the V3 neuron underlies basic standing behaviour in intact animals - and that this can be harnessed to restore standing in mice after spinal cord injury."
Fall 2025 grant recipients
Bennett's is one of 23 U of A research projects to receive a total of $18,120,679 from the Canadian Institutes of Health Research through its Fall 2025 Project Grants and Priority Announcements:
Robin Clugston, Stephane Bourque, Faculty of Medicine & Dentistry
$944,775
Margie Davenport, Faculty of Kinesiology, Sport, and Recreation
International practice and policy for pregnant and postpartum athletes
$202,726
Yinfei Duan, Carole Estabrooks, Faculty of Nursing
$325,125
Jason Dyck, Faculty of Medicine & Dentistry
$1,281,375
Shokrollah Elahi, Faculty of Medicine & Dentistry
Decoding Long COVID in women: Immunological mechanisms and clinical implications
$1,040,400
Janet Elliott, Faculty of Engineering
Cryopreservation of in vitro models of the blood-brain barrier
$937,125
Dean Eurich, School of Public Health
First Nations Catalyzing Resources and Relationships for the Uptake of Screening and Healthcare for Cancer (FN CRRUSH Cancer) (Priority Announcement)
$100,000
Victor Ezeugwu, Faculty of Rehabilitation Medicine
Behavioural Intervention and Guided Stepping Training Early Post-Stroke (BIG STEPS)
$787,950
Mark Haykowsky, Faculty of Nursing
$634,950
Ashley Hyde, Faculty of Nursing, Farhad Peerani, Puneeta Tandon, Faculty of Medicine & Dentistry
$240,975
Mahesh Kate, Brian Buck, Faculty of Medicine & Dentistry
$730,576
Tony Kiang, Faculty of Pharmacy and Pharmaceutical Sciences
$1,139,850
Svetlana Komarova, Faculty of Engineering
Unravelling osteoclast regulation by collagens: Mechanisms and therapeutic potential
$680,850
Darren Lau, Faculty of Medicine & Dentistry
$1,185,752
Salima Meherali, Faculty of Nursing, Simone Lebeuf, Faculty of Medicine & Dentistry
$902,700
Elisavet Papathanasaglou, Faculty of Nursing
Co-creating a person-centred strategy to manage psychological stress in critically ill patients (Priority Announcement)
$100,000
Jason Plemel, Fabrizio Guiliani, Faculty of Medicine & Dentistry
Interferon responsive microglia regulate remyelination
$1,361,700
Michael Stickland, Faculty of Medicine & Dentistry
Cardiopulmonary complications of electronic cigarettes
$979,200
Alan Wilman, Faculty of Medicine & Dentistry
New susceptibility MRI methods for progressive multiple sclerosis
$837,675
Stephanie Yanow, School of Public Health
A molecular fever panel to support malaria elimination, management of fever, and arbovirus surveillance in a resource-limited district of Colombia (Priority Announcement)
$100,000
Toshifumi Yokota, Faculty of Medicine & Dentistry
$1,147,500
Dawei Zhang, Faculty of Medicine & Dentistry
Dissecting the cell type-specific role of MT1-MMP/MMP14 in the development of liver fibrosis
$1,067,175
