A new discovery from Milena Russo in the Liu Lab at UTM upends thinking about the way the brain perceives objects against a moving background.
Have you ever missed a road sign while driving because your attention was drawn to the motion of traffic around you? This could be because of neural pathways laid down in our ancestors long ago to resolve predators or prey in the drive to survive.
Looking beyond the cortex
Milena Russo in Baohua Liu‘s lab investigates how the brain interprets visual information in dynamic environments for her PhD. When she started, the field thought that the effects of background motion on visual perception arise primarily from the cerebral cortex.
Yet Russo was intrigued by observations that challenged this idea and implied a role for the brainstem, located at the back of the brain. Her discoveries from this insight are published in Nature Communications as “An inhibitory brainstem pathway reduces visual detection during background motion”
“There’s been evidence of this ‘motion modulation’ phenomenon even in non-mammalian species,” Russo explains. “but animals like fish or birds don’t even have a cortex.” In humans, the cortex is the wrinkly part on the surface on the brain.
“The fact that this phenomenon exists in non-mammalian species was really interesting,” concluded Russo, “because there must be a more ancient mechanism aside from the cortex that is contributing to this phenomenon.”
The brainstem is an ancient region of the brain, which controls innate visual responses, such as eye movement stabilizing gaze. Russo’s own intriguing finding on the brainstem came to light as a pioneering study in Professor Liu’s lab.
Russo initially performed tracing of the brainstem neural circuitry in the mouse brain. She found that inhibitory neurons in the brainstem region known as the nucleus of the optic tract (NOT) project densely to the superior colliculus (SC), highlighting an unexplored pathway involved in visual processing.
These observations were difficult to ignore because the NOT is a visual structure known for its capability of motion processing and the SC is implicated in visual perception, “but we didn’t really understand what the role of this pathway could be,” notes Russo. “That’s kind of where we found our little in, and then where we expanded this research.”
Resolving the NOT-SC circuit
Russo and her colleagues devised a novel experimental approach, training mice to respond to a flashing dot, which depends on SC activity. The team found that under normal conditions the mice were slower to respond to the dot against the moving background in comparison to static background. SC activity was correspondingly suppressed by the moving background.
To assess the role of the previously unexplored pathway connecting the NOT and SC in this background motion modulation, Russo turned to recent advances in optogenetics: light sensitive channels or pumps that can be used to activate or silence neurons. With the help of these tools, Russo used light to selectively silence the inhibitory projections from the NOT to SC.
Russo asked: “If we block this pathway, what is going to happen in the downstream region? That will give us a clear indication of how this pathway functions in a normal physiological scenario.”
When the inhibitory pathway to the SC was silenced, visual detection of the dot against a moving background improved and SC activity was enhanced. This revealed that background motion engages the NOT-SC pathway to suppress visual responses in the SC and in turn impair SC-mediated visual detection.
For Russo, this momentous result was a turning point: “It was the first moment where I could kind of see a paper coming together.” She went to lunch with a friend that day and excitedly asked, “Guess what I found?”
Shaping what we see today
Her finding was surprising for neuroscientists because the evolutionarily ancient brainstem has traditionally been associated with reflexes, an innate behaviour, rather than with processing perceptions.
Instead Russo’s work shows that a brainstem circuit actively influences what animals see. In everyday life, these circuits may help explain why important visual objects such as a road sign can be overlooked when surrounded by the busy world.
There are clinical implications for this work as well. Some people are affected by motion blindness and cannot see moving objects. Motion processing defects can also be seen in people affected by autism or schizophrenia. Russo’s work suggests that developing treatments to alleviate these conditions should also consider subcortical circuits as potential targets.
A bright future for visual neuroscience
As this paper was in press, Russo earned an award for Best Talk at CSB Research Day, recognizing the significance of her findings and her ability to communicate them to a broad scientific audience.
Liu sees these achievements as important milestones in a student’s development. As students begin collecting data and presenting their findings, “they are basically driving themselves to go forward,” says Liu. “I’m seeing a maturation, or growth of a young generation of scientists.”
The study also suggests an important question to pursue. “I want to know why NOT inhibits SC; what are the physiological effects that are occurring to cause inhibition,” says Russo.
Her future work will investigate how and why inhibitory NOT neurons silence activity in the superior colliculus during background motion.
Congratulations on this paradigm-shifting paper!