The human cerebellum is only 10% of the total volume of the brain, but it contains over 50% of the neurons in the entire nervous system. The cerebellum not only coordinates movement, but also influences human thinking and emotions. In the process of exploring the diversity of cerebellar function, especially in analyzing how the cerebellum participates in and influences cognitive function and emotional processing, a key axis has been discovered - the sensory motor connectivity (SA) axis. This axis helps to explain the complexity of cerebellar functional hierarchy. However, most studies have focused on exploring the generation and significance of the SA axis in the human cerebral cortex, with little research on how the SA axis is formed in the cerebellum and its biological basis.

Recently, Fan Lingzhong, et al. from the Brain Atlas and Brain like Intelligence Laboratory of the Institute of Automation, Chinese Academy of Sciences, further explored the biological basis of the hierarchical structure of human cerebellar function on the basis of the genetic evidence behind the previously discovered functional heterogeneity of human cerebellum. The related research results are titled Spatial Molecular profiles Shape of the Human Cerebellar Hierarchy Along the Sensor Association Axis and published in Cell Reports. This research system integrates cross scale and multi omics information, providing a panoramic view of the spatiotemporal molecular spectrum behind the cerebellar SA axis - from genetic characteristics, intermediate molecular patterns, cell types, biological processes, to spatiotemporal developmental patterns, disease correlations, evolutionary correlations, and interactions between the brain and the brain.

This study attempts to answer the following scientific questions: whether significant changes in gene expression are involved in shaping the cerebellar SA axis; What intermediate biological principles mediate the formation of the SA axis, and whether there is a connection between these molecular matrices and cerebellar related neurodevelopment, evolution, and neuropsychiatric disorders; Considering that the functional diversity of the cerebellum mainly stems from its interconnection with brain structures, how the spatial molecular characteristics of the cerebellum interact with the cerebral cortex at the genetic and functional connectivity levels.

In response to these issues, this study combined human brain transcriptome spectra and multimodal human brain imaging data, and found that gene expression can significantly predict the cerebellar SA axis. At the same time, a group of significant genes were identified through spatial autocorrelation preservation permutation. For the first time, gene set variation analysis was introduced into brain imaging transcriptome association analysis, revealing the spatial molecular features of genes used to organize cerebellar functional hierarchy. These spatial molecular features are closely related to neurological and psychiatric dysfunction and human brain evolution. In addition, the interaction between the cerebellum and the brain at the genetic and functional connectivity levels is consistent with the SA axis of the cerebral cortex and cerebellum, providing a possible basis for the consistency of the SA axis between the large and small brain regions.

In summary, this study provides evidence of the spatiotemporal molecular characteristics that make up the human cerebellar SA axis, revealing the micro macro intersecting organizational patterns in which the cerebellum forms the SA axis. Research has found through the integration of multi-level information on human cerebellar function that along the SA axis, the expression of genes related to cerebellar neurotransmitter transmission increases, differences in developmental processes occur, the influence of evolutionary biological processes increases, and the association with mental illness increases.

The research work has been supported by the Science and Technology Innovation 2030- "Brain Science and Brain like Research" major project and the National Natural Science Foundation of China.

Paper link:论文链接



Research ideas on spatiotemporal molecular spectra behind the hierarchical structure of human cerebellar function