WHOLE-BRAIN SPATIOTEMPORAL MAPPING OF CIRCUIT MATURATION DURING DEVELOPMENT

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Description

Brain development is a highly dynamic and asynchronous process, characterized by the sequential maturation of functional circuits throughout the brain. The timing and mechanisms driving circuit maturation remain largely elusive due to an inability to identify and map maturing neuronal populations. This process is often disrupted in neurodevelopmental disorders, leading to behavior deficits. However, such disruptions at the level of synapses and circuits typically do not result in changes to gross brain structures. To address these challenges, we have developed DevATLAS (Developmental Activation Timing-based Longitudinal Acquisition System), a novel reporter system designed to capture neuronal populations during activity-dependent circuit maturation and track their integration into functional neural circuits. By combining DevATLAS with an advanced whole-brain imaging and analysis pipeline, we have created the first comprehensive spatiotemporal map of circuit maturation. Importantly, DevATLAS can serve as a high-throughput platform to pinpoint when and where circuit maturation is disrupted in mouse models of neurodevelopmental disorders, such as fragile X syndrome (Fmr1 KO mice). DevATLAS and the accompanying database provide a much-needed resource for the neuroscience research community and accelerate investigations into the mechanisms underlying brain development and disease.

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This work is licensed under a Creative Commons Attribution 4.0 International License as of December 1, 2023.

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