Long-Range Plasticity of Neuronal Networks in the Adult Brain

Informations projet

LongPlaNet

N° de convention de subvention: 845685

DOI

10.3030/845685

Projet clôturé

Date de signature de la CE 10 Avril 2019

Date de début 1 Octobre 2019

Date de fin 11 Novembre 2021

Financé au titre de

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Coût total

€ 184 707,84

Contribution de l’UE

€ 184 707,84

Coordonné par

INSTITUT DU CERVEAU ET DE LA MOELLE EPINIERE
France

Periodic Reporting for period 1 - LongPlaNet (Long-Range Plasticity of Neuronal Networks in the Adult Brain)

Période du rapport: 2019-10-01 au 2021-09-30

Résumé du contexte et des objectifs généraux du projet

LongPlaNet (Long-Range Plasticity of Neuronal Networks in the adult Brain) aimed to study the plastic potential of the adult brain. Modifying the sensory experience (ex. permanently removing the tactile whiskers in mice) we challenge the brain to adapt. When this happens in the younghood, neuronal connections are reshaped to optimize the use of the affected brain regions. However, when sensory experience is modified during the adulthood, no major structural readjustments seem to take place, and although cross-modal adaptation to sensory loss or motor learning are present in the adult age, the mechanisms underlying these processes are poorly understood. LongPlaNet challenged this dogma, studying in detail the nature of structural plasticity in the adult brain. Understanding the potential of the adult brain to experience plastic readjustments will set the basis do further understand axonal stability and degradation in the adult brain, a key process in the search for new therapeutic targets for neurodegenerative diseases, traumatic injuries, or psychiatric diseases in our aged societies.

The overall objectives of the action are summarized as:
- Analysis of changes in long-range connectivity after sensory deprivation.
- Study of the transcriptional changes after sensory deprivation.
- Longitudinal assessment of circuit function.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

During the duration of the action, I implemented 3 work packages (WP) that correlate with the three main objectives of the project:
The first WP aimed to study changes in long-range connectivity. I used two strategies: study of axonal densities by unbiased whole-brain pNFH mapping, and study of inter-area axonal connectivity with viral tracers.
The second WP consisted in the generation of a database of genes differentially expressed after sensory deprivation.
Finally, the third WP studies the functional consequences of sensory deprivation in vivo, combining Ca+2 imaging with fiber photometry with advanced behavior analysis.
The major founding of the action includes evidence of structural readjustments in long-range projecting axons and vasculature in the long-term. The results will be disseminated in a manuscript planned to be finished in the second semester of 2022.
The implementation of LongPlaNet required the development of bioinformatic tools for the analysis of whole-brain datasets of axons, and building an entire setup with the associated software for synchronized analysis of Ca+2 neuronal signaling, behavior tracking and high-speed whisker movements. All these resources are potentially exploitable and will be disseminated at the same time than the main manuscript of the action.

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

So far, LongPlaNet has already generated evidences that long-range structural readjustments are possible in the adult brain, even when sensory experience is modified in the adulthood. By the end of the project I expect to have the broad picture correlating changes in connectivity, vasculature and activity to set the basis for further basic and clinical research focused in the molecular regulators and, therefore, potential pharmacological targets of the system.

LongPlaNet required the development of bioinformatics tools for whole-brain connectivity analysis