SubsidieMeestersSculpting circuits and behavior by developmental neuronal remodeling
This project aims to integrate molecular, cellular, circuit, and behavioral aspects of neuronal remodeling in Drosophila's Mushroom Body to understand its impact on circuit architecture and behavior.
Projectdetails
Introduction
Neuronal remodeling is a conserved strategy to refine neural circuits during development. Defects in remodeling have been associated with neuropsychiatric disorders, but direct mechanistic causality is lacking.
Significance of Neuronal Remodeling
Despite its fundamental significance, how remodeling of neuronal processes affects circuit architecture and function, and how this ultimately shapes behavior, is not only unknown but also extremely challenging to study in complex organisms.
Research Focus
Our lab is a world leader in the molecular mechanisms of neuronal remodeling. We use the stereotypic remodeling of the Drosophila Mushroom Body (MB), a complex circuit within the fly brain, as a powerful genetic model to study this question.
Recent Discoveries
Recently, we uncovered that MB remodeling is coordinated at the circuit level. Furthermore, we generated a detailed expression atlas of MB neurons during development, which highlighted genes and pathways mediating cell-cell interactions as prime remodeling regulators.
Research Objectives
Thus, our discoveries suggest that the time is ripe to take on the challenge of integrating the molecular, cellular, circuit, and behavioral aspects of remodeling. The MB is a perfect system for this due to its well-characterized structure and function.
- Objective 1: To build upon our developmental expression atlas to identify molecules that mediate cell-cell interactions during remodeling.
- Objective 2: To investigate how specific genetic/cellular perturbations of remodeling impact overall circuit architecture and connectivity.
- Objective 3: To take a new direction for the lab by using behavioral readouts of MB function to understand how specific genetic perturbations of remodeling and connectivity affect circuit function and behavior.
Expected Outcomes
While each objective is independent and expected to yield high-impact discoveries by itself, it is their combined implementation that is expected to provide the first holistic picture of neuronal remodeling from molecules to cells, circuits, and function.
Financiële details & Tijdlijn
Financiële details
| Subsidiebedrag | € 2.500.000 |
| Totale projectbegroting | € 2.500.000 |
Tijdlijn
| Startdatum | 1-5-2022 |
| Einddatum | 30-4-2027 |
| Subsidiejaar | 2022 |
Partners & Locaties
Projectpartners
- WEIZMANN INSTITUTE OF SCIENCEpenvoerder
Land(en)
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