Social deficits attract so much attention in the study of autism spectrum disorder, it鈥檚 easy to forget there are motor learning deficits during early childhood as well. For autistic kids hoping to throw a ball around the schoolyard and connect with classmates, these physical skill differences can isolate a child further.
In a new study published in researchers from the University of Ottawa鈥檚 Faculty of Medicine have closed in on the neurological underpinnings of the motor learning delay. Dr. Simon Chen鈥檚 lab in the Department of Cellular and Molecular Medicine used a mouse model of autism to demonstrate a shortage in the amount of the neurotransmitter noradrenaline being released into the brain鈥檚 primary motor cortex.
Dr. Chen鈥檚 lab identified the problem originating some distance away in an area of the hindbrain called the locus coeruleus, which is known as a center of motivation, alertness, and attention.
What is the locus coeruleus?
鈥淭he locus coeruleus is the area in the brain that releases noradrenaline 鈥 or adrenaline 鈥 which makes you more alert. In the mouse model of autism, we found that in the motor cortex there is a lack of adrenaline鈥檚 innervation to the area which caused them to have delayed motor learning. The lack of basal level of adrenaline in the cortex causes them to have this delayed learning.鈥
By delay in learning you mean it takes them longer to learn a task?
鈥淵es, and the implication is similar for kids with autism. They normally behave the same whether reaching to grab something or playing ball or catch 鈥 they learn at a slower pace compared to kids of the same age, which could cause them to feel more distant and perhaps prefer not to play with them.
鈥淲ith autistic kids, we sometimes think that an aspect of this delayed motor learning is a result of social deficits and dysfunction: that they simply don鈥檛 want to play with the other kids. But it might be because they鈥檙e learning how to play these games slower than the other kids, which is why they鈥檙e distancing themselves from them.
鈥淲e asked: what is the source of this? Is it occurring because of deficits in the locus coeruleus, or is the cause purely in the motor cortex?鈥
How did you proceed?
鈥淢y background is studying the mechanism in the brain involved in motor learning. I thought it would be important to investigate disorders associated with motor learning. In my literature research, I found many cases of autistic kids displaying this type of delayed motor learning. So, we thought to try to see whether we can find that in mice.
鈥淲e performed live imaging into mice鈥檚 brains, and we found the brains of the adolescent mice we used showed a delay in removing old substrates while forming new ones which causes confusion to the brain causing an effect we describe as low signal-to-noise ratio (old memories are noise). When you are not removing the unnecessary synapses (old memories) you have higher noise, and we think the brain doesn鈥檛 know what signal to process because of its delay of removing the unnecessary synapses. So, the mouse is slower learning what the right movement is.
鈥淭hink of it as you and I go play golf and we hit the ball many times. With a good signal-to-noise ratio in the brain, I will remember the movement when I hit the ball far. But if I have high noise and low signal-to-noise ratio, I鈥檒l hit the ball many times without knowing which movement is good for me, meaning it will take me longer to differentiate what鈥檚 the right movement for a good golf swing.鈥
What did you have the mice do to discover this?
鈥淢ice like to run so we had them learning how to run on a spinning disk. Their head was fixed so they needed to learn how to adjust their body to run and that鈥檚 what we were trying to measure. Initially, they had a hard time controlling their body position. But after 12 days, they learned how to control their body and are now able to run smoothly on the rotating disk.
鈥淲hen we injected an artificial drug in the belly to increase the noradrenaline release globally, the mice鈥檚 behavior was rescued. But then we asked ourselves 鈥榟ow do we know it鈥檚 not just because the mouse is paying more attention when they are doing the task and that鈥檚 why they do it faster?鈥 We then injected the artificial drug locally in the motor cortex to activate the axons of the axons from locus coeruleus, and the mice鈥檚 behavior was again rescued.
鈥淭his suggests that it鈥檚 not because the mouse is more focused but, rather, because of the drug that they learn the task better. The noradrenaline is lacking in the motor cortex and if we supplement enough noradrenaline in the motor cortex, then the mouse will be able to learn.鈥
What should we take away from your study?
鈥淜ids with autism tend to show a delay in motor learning which is normally overlooked since it is put down to social deficits. But it could be they are learning how to play but slower. Now it鈥檚 about whether we can help the kids to learn these motor skills faster to compensate for some of the social deficits we think they鈥檙e having.
鈥淭he mouse鈥檚 motor skills improved quicker by boosting the noradrenaline in the motor cortex; maybe one day we can find a treatment to boost the noradrenaline in a patient and that will also help them learn a new motor skill quicker.鈥
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