Left-Right Brain-Wide Asymmetry of Neuroanatomy in the Mouse Brain

Left-right asymmetry of the human brain is widespread through its anatomy and function. However, limited microscopic understanding of it exists, particularly for anatomical asymmetry where there are few well-established animal models. In humans, most of the brain shows subtle, population-average, regional asymmetries in cortical thickness or surface area. In addition, a macro-scale twisting called the cerebral petalia exists in which the right hemisphere protrudes anteriorly relative to the left. Here, we ask whether neuroanatomical asymmetries can be observed in mice, leveraging 6 different neuroimaging cohorts of animals from 5 different research groups (∼3,500 animals in total). We found an anterior-posterior pattern of volume asymmetry in mice, where anterior regions are larger on the right while posterior regions are larger on the left. This pattern appears driven by a similar trend in surface area asymmetry and is supported by a concordant pattern of positional asymmetries. The cerebral hemisphere as a whole appears shifted anteriorly on the right while the brainstem and cerebellum appear shifted anteriorly on the left. These results together indicate a small torsion of the brain is present in mice, similar to the cerebral petalia in humans. By establishing a signature of anatomical brain asymmetry in mice, we aim to provide a foundation for future studies to probe the mechanistic underpinnings of anatomical brain asymmetry seen in humans – a feature of the brain with extremely limited understanding.