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Mechanisms of neuronal network remodeling in the adult mammalian brain

Periodic Reporting for period 3 - NeuroRemod (Mechanisms of neuronal network remodeling in the adult mammalian brain)

Période du rapport: 2021-04-01 au 2022-09-30

Over the course of our life, experiences shape the way our brain process information. As we learn or adapt to changes, be they intrinsic or extrinsic, new connections are formed between neurons as others are pruned, while existing connections can be strengthened or weakened. The constant remodeling through diverse means of the flow of neural information is known as plasticity. The purpose of the NeuroRemod project is to study the phenomena of structural brain plasticity in adults at the axon level and neural networks in the whole brain. The structural support of cerebral plasticity in the adult brain is not well characterized, and looking into into it precisely is a prerequisite to tailor strategies for cognitive rehabilitation in pathological contexts (stroke, brain injuries...).

We use as a model system the circuit for processing sensory information from whiskers in mice. Plasticity is induced by surgical removal of the whiskers and infra-orbital nerve in adults, and the study of this phenomenon was divided into three research objectives:
1. Characterize the anatomical and connectivity changes induced by the loss of sensory information in adults at the whole brain level
2. Establish molecular mechanisms to control axonal plasticity in adults
3. Explore the role of cerebral vasculature in the control of adult neuronal plasticity
- Since the beginning of the project, we have developed key technologies necessary for the precise measurement of network plasticity in the adult brain. We implemented quantification strategies for the 3D mapping of axons, enabling us to measure precisely this phenomenon with an unprecedented resolution.
- We also invented a novel mapping tool for the vascular system, which produced one of the first complete map of the brain vascular system at the capillary level. Using this technology, we mapped the changes imposed on the vascular structure of the brain after a sensory loss (Kirst et al. Cell 2020).
- We now clearly defined the timeframe and locations of adult structural plasticity in the somatosensory cortex, enabling us to investigate now the rules and mechanisms of plasticity in this system.
- We expect that our unique vascular mapping tool will reveal unsuspected interactions between neuronal activity and vascular topology in the adult brain
- We will now be able to describe precisely the type of neurons undergoing plastic rearrangement in the cortex, and which axonal branches are susceptible to this reorganization.
- This level of description will facilite the description of molecular pathways involved in branch pruning.
Project summary: mapping technologies developed during the first half of the project