The cerebellum, often called the “little brain,” is a distinct region located at the back of the brain, beneath the cerebrum. It coordinates various brain functions. Understanding its workings is important for overall brain health and function. The mouse cerebellum has emerged as a valuable model for researchers.
Structure and Fundamental Roles
The mouse cerebellum exhibits a highly organized anatomical structure, characterized by a complex, folded outer layer known as the cerebellar cortex. This cortex is divided into multiple lobules arranged along its anterior-posterior axis, often identified by Roman numerals. Beyond these lobules, the cerebellum also features medial-lateral divisions, including a central vermis and larger lateral hemispheres.
Specific cell types reside within this architecture. Purkinje cells, large and highly branched neurons, are a distinctive feature of the cerebellar cortex, forming a single layer and playing a significant role in its output. Granule cells are also found here and are far more numerous. The cerebellum is widely recognized for its involvement in motor coordination, enabling smooth and precise movements, and maintaining balance. It also contributes to motor learning and certain cognitive processes.
Advantages of Mouse Models
Mice are extensively used as model organisms in neuroscience, particularly for studying the cerebellum. Their genetic makeup shares significant similarities with humans, with an approximately 85% overlap in genome similarity. This genetic resemblance allows researchers to study human diseases and conditions in a laboratory setting.
Mouse genetics are easily manipulated. Researchers can introduce specific genetic changes, such as “knockout” mice, to investigate the impact of individual genes on neurological function and disease progression. Their relatively short life cycles of about two years allow for quicker study of age-related diseases. Mice are also cost-effective to maintain and breed, facilitating large-scale experiments. The ability to precisely control environmental factors like diet and stress levels helps establish cause-and-effect relationships, which is challenging in human studies.
Advancing Neurological Understanding
Research on the mouse cerebellum has provided insights into various neurological conditions, aiding understanding of disease mechanisms and therapeutic strategies. For neurodegenerative diseases like hereditary cerebellar ataxias, mouse models such as the “Lurcher mouse” have investigated functional impairments. Studies in mice have also explored the cerebellum’s involvement in Alzheimer’s disease, highlighting its role in cognitive function and suggesting that stimulating the cerebellum could improve symptoms. Researchers have identified potential drug candidates, like a combination of two cancer drugs, that reduced brain degeneration and restored memory in mouse models of Alzheimer’s disease by reversing damaged gene behavior.
The mouse cerebellum has also contributed to understanding neurodevelopmental disorders like autism spectrum disorder (ASD). Post-mortem studies in humans with ASD have shown a reduced number and density of Purkinje cells in the cerebellum, a finding often replicated in mouse models of ASD. Deleting the autism-linked gene CNTNAP2 in mice leads to distinct cellular and electrical changes in cerebellar Purkinje cells, including a slower rate of complex spike firing. Mouse models with specific genetic disruptions, such as in the Scn8a gene, have demonstrated behavioral traits related to ASD and anxiety, alongside progressive cerebellar atrophy and loss of Purkinje cells.
Beyond neurodevelopmental and neurodegenerative disorders, mouse models have also informed research into injury recovery. Studies using mice have explored how deep cerebellar stimulation of the lateral cerebellar nucleus can enhance cognitive recovery after traumatic brain injury (TBI) by activating ascending projections to the thalamus and upregulating thalamocortical activity. Research also suggests that early re-engagement in tasks after brain injury in mice can be more beneficial for recovery than prolonged rest, indicating the brain’s capacity to adapt through activity.