To enabled the exploration of adult structural plasticity, we have developed during this project key technologies that were 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. For this, we used both viral tracings and structural axonal markers. The use of structural markers enabled us to clearly define the timeframe and locations of adult structural plasticity in the whole brain. We documented molecular modifications to thalamocortical axons following sensory deprivation. The manuscript for these findings is under preparation.
We also developed 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). Following up on the possibilities offered by this tool, we generated a brain atlas of vascular development, and studied how it is altered by sensory loss (manuscript submitted, data available at
https://lambada.icm-institute.org(se abrirá en una nueva ventana)).
In another manuscript, we used these mapping tools to document how sensory deprivation induce long-term vascular loss in the whole brain, revealing life-long interactions between neuronal activity levels and vascular topology. These results may be important in the context of neurodegenerative diseases, where minute alterations to network activity may influence in the long-term the stability of the vascular network. These results are now being assembled in a manuscript to be submitted soon.
Lastly, we also studied neuronal adult plasticity in the context of changes to internal states, by using pregnancy as a model. In this work, we documented the role of progesterone on the plasticity of a small population of neurons, in the Edinger Westphal nucleus, which we had identified via an unbiased screen. We found that plasticity in the activity patterns of this group of neurons was essential for the onset of maternal behavior, such as nesting, during pregnancy (Topilko et al. Neuron 2022).
Overall, the project enabled us to create advanced tools for the brain-wide study of post-natal plasticity. It helped us find clear instances of structural and functional plasticity, both on neuronal and vascular networks, revealing unsuspected interactions between neuronal activity and vascular topology in the adult brain. This level of description will facilitate the description of molecular pathways involved in branch pruning.
