New study uncovers another role for the cerebellum, offering clues about autism
Research from the ASU Department of Psychology suggests a new role for the cerebellum during a critical period of development that happens from infancy to early childhood. Photo by Tara Winstead/Pexels
There is a window of time, a critical period, during infancy and early childhood when the brain learns how to process information — what different objects look like, parsing sounds that make up language and how to navigate social interactions.
If the brain is not exposed to information during this critical period, some abilities never develop. For example, this is why some people who learn English as an adult cannot hear or pronounce the difference between “R” and “L” sounds.
New research from the Arizona State University Department of Psychology has shown that the cerebellum, a structure at the back of the brain that until recently was thought to contribute only to coordination and movement, is more involved in the brain’s critical period than previously understood.
A disruption in the interactions between the cerebellum and the rest of the brain during the critical period led to reduced social behaviors, especially in males, according to the work, which used animal models.
The cerebellar disruption also resulted in structural and functional changes in the cortex, the outermost areas of the brain, and subcortical regions located deep within the brain.
“During the critical period, the type of input the cerebellum is getting and the output it is sending affects more brain regions than previously thought. Our findings show that the cerebellum influences cortical and subcortical circuits that are involved in reward processing and social behaviors,” said Tristan Lyle, a psychology graduate student at ASU and first author on the study.
The study has been published in Molecular Psychiatry.
We think that the cerebellum acts like a metronome, a timer, that contributes to the balance between excitatory and inhibitory functions in the brain. We really need to understand what other brain areas are involved because it could lead to relief of symptoms of neurodevelopmental disorders involving the cerebellum.
Jessica VerpeutAssistant professor of pyschology
A possible role in autism
The researchers used a technique that merges chemistry and genetics to inactivate the lateral cerebellar nuclei, a group of neurons deep within each of the cerebellum’s two lobes.
These cerebellar cells were shut down during a time that corresponds to infancy in humans and that encompassed the critical period.
The effects were far reaching throughout the rest of the brain.
The lack of activity from lateral cerebellar nuclei affected neuronal activity in the ventral tegmental area, a brainstem region where dopamine neurons are located, the nucleus accumbens and the anterior cingulate cortex. A molecular marker showed decreased activity in this circuit, which is known to be involved in reward processing.
Inactivating the lateral cerebellar nuclei during the critical period also caused pronounced behavior changes — abolishing social behaviors in males.
These findings have implications for the understanding of autism, the researchers said, because the cerebellum is the most commonly affected brain region in the disorder.
If a baby experiences an injury to their cerebellum, as can happen during birth from stroke or lack of oxygen, their odds of being diagnosed with autism spectrum disorder increase by a multiple of 40.
“Autism is more likely to be diagnosed in the male population, which could be a result of diagnostic criteria that are skewed toward males. However, our findings show that the phenotype for social behavior in the paradigm we used was skewed toward males being affected by the cerebellum perturbation,” said Jessica Verpeut, assistant professor of psychology at ASU and senior author on the paper.
Glowing cells show cerebellum affects cortical neuron structure
The researchers used proteins that fluoresce, or glow, neon yellow to examine whether inactivating the lateral cerebellar nuclei affected the structure of neurons in the cortex.
In the anterior cingulate cortex, the dendrites were denser and more complex than if the lateral cerebellar nuclei had not been turned off. Dendrites are neuronal appendages that can look like tree branches and are the gateway for incoming information to neurons.
“These brain regions are not acting by themselves; they are all connected and are impacting each other across the lifespan,” Verpeut said. “We think that the cerebellum acts like a metronome, a timer, that contributes to the balance between excitatory and inhibitory functions in the brain.
ASU alumni Kristin Masho Elbeh, Henrique Vieira and Daniel Chambers — now a neuroscience graduate student — were co-authors on the paper. This work was funded by the State of Arizona and U.S. Department of Health and Human Services, National Institute on Aging, the Institute for Mental Health Research, the Institute for Social Science Research, the Nancy Eisenberg Junior Faculty Scholar Award, the Arizona Department of Health Sciences, the Arizona Alzheimer’s Disease Research Center Fellows Program, and the Arizona Alzheimer’s Consortium.
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