The researchers of the Institute of Neurosciences (CSIC-UMH) mapped for the first time, on animal models, how connections from the cerebellum to the braindefining stages of particular vulnerability in which genetic or environmental factors could alter neuronal maturation. These critical windows could influence the origin of autism, schizophrenia and others neurodevelopmental disorders.
In this way, “the first complete map of connection development from the cerebellum to the rest of the brain, work that reveals when and how these neural pathways form, develop and refine during the early stages of life.
The researchers, who identified in mice “critical windows of vulnerability in which genetic alterations or environmental factors can affect the maturation of these circuitswhich could contribute to the origin of neurodevelopmental disorders such as autism and schizophrenia.
He cerebellumtraditionally associated with the control of movement, has demonstrated in recent years an essential role in functions such as learning, emotions and social behavior, explains the UMH. However, until now, “it was unclear precisely when it began to communicate with other regions of the brain, a key interaction for these functions.”
This gap is filled by the study published in the journal PNAS and led by CSIC researcher Juan Antonio Moreno Bravo, head of the group. Development, connectivity and function of cerebellar circuits. The work was funded by the European Research Council (ERC), the National Research Agency (AEI) of the Ministry of Science, Innovation and Universities and the Severo Ochoa Program for Centers of Excellence.
As Moreno Bravo explains, “the first cerebellar projections already appear in the embryo, when axons begin to connect to several brain areas.” Following, These connections expand massively during accelerated brain growth. in the prenatal and perinatal stages. Finally, during the first weeks after birth, they go through a period of refinement, consolidating the definitive connections that support cerebellar function in adulthood.
“This stepwise sequence allows us to identify moments when the cerebellum could influence other regions of the brain even before it is fully mature,” said the researcher, who highlighted the importance of these first steps Understand the organization of brain architecture.
The results suggest that the cerebellum may exert an earlier and more intense influence on the formation of brain circuits than previously believed: “Our work rethinks the classic view of the cerebellum as a late modulator of movement. In reality, he starts building his network very early and could actively contribute to the formation of complex circuits from the early stages of development,” said Moreno Bravo.
The study provides “an unprecedented reference tool for studying how early experiences, genetic mutations or environmental conditions can interfere with this process.” According to the authors, “understanding these critical windows will allow advance the study of alterations of cerebellar origin linked to neurodevelopmental disorders”.
This advance was possible thanks to the combined use of genetic techniques and cutting-edge three-dimensional imaging technologies applied to the entire brain. Using specific fluorescent markers, neurons in the deep cerebellar nuclei (the main output pathway of the cerebellum) were marked and, subsequently, the path of the axons has been reconstructed in 3D from their region of origin to their region of destination.
“Visualizing these projections in 3D and observing how they emerge and unfold in the brain has been fascinating,” said Raquel Murcia Ramón, first author of the study. “Many of these connections have never before been observed with such precision, and tracking them over time has allowed us to piece together the full history of these circuits.”
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