Tiny antenna-like organelles once thought to be relics from our distant past appear to be play a crucial role in keeping time, according to a recent study on mice by researchers at the University of California, Irvine (UCI) in the US.
Known as cilia, the microtubule projections are found in the more complex branches of the tree of life, including on many of our own cells.
Where they often play a role in movement, either pushing cells around or moving materials close to their surface, most in the human body — described as primary cilia — are non-motile.
Initial investigations more than a century ago considered these types of structures vestigial. Today, many primary cilia are recognized as part of a signaling hub system that ensures the body adapts and responds appropriately.
Although distinct roles of primary cilia in receiving and responding to sensory information have been established, little is known about how these organelles fit with higher-order cognitive functions occurring in the brain.
Part of the job of the area of the brain known as the striatum is to act as this central clock, coordinating motor movements, learning, planning and decision-making. It is also important for managing working memory and maintaining attention.
For their study, the researchers used a gene-engineering technique to remove striatal cilia in mice, which had a dramatic effect.
While the mice were still able to retain long-term memories and habitual or already-learned motor skills, several negative effects were observed after cilia removal.
The rodents proved unable to learn new motor tasks and showed repetitive motor behavior and noticeable delays in decision making. Their ability to quickly recall location and orientation information, and their ability to filter out irrelevant environmental sensory information, were negatively affected.
Several tests and exercises were performed on the mice to draw these conclusions, including leading the animals through mazes and testing their ability to recognize objects and locations.
“Successful performance of working memory, attention, decision making and executive function requires precise and accurate timing judgment, usually within a millisecond to a minute,” says UCI neuroscientist Amal Alachkar.
“When that capacity is compromised, it means you lose the ability to quickly modify behavior in response to changes in external stimuli and you can’t sustain appropriate, goal-directed motor responses.”
Clearly, all the effects of ciliary removal share a common feature: the loss of the ability to rapidly change behavior in response to environmental changes within an appropriate time frame.
How the results of this study relate to humans is not yet fully known, but it is likely that the cilia of the human brain work similarly to those of mice. The researchers are already working on follow-up studies to further analyze the relationship between cilia and time perception.
The finding not only improves our understanding of how we perceive the world, but could also help us solve the problem in case our view of time goes wrong.
Impaired time perception and erroneous time judgment is a feature found in numerous mental and neurological disorders, including schizophrenia, Parkinson’s disease, Tourette’s syndrome, autism spectrum disorder, and Huntington’s disease.
“Our results may open new avenues for effective intervention through cilia-targeted therapies for treatment,” says Alachkar.
“Our ongoing work is focused on understanding the mechanisms by which cilia regulate timekeeping and developing targeted therapies to ameliorate behavioral deficits.”
The research has been published in Molecular Neurobiology.