The Larva Box
The projects goal is to develop specific simulation-based methods to infer modifications of neural circuit
structure and dynamics from observed behavior alterations. By exploring the effects of parameter modulation, our model will improve our understanding of previously identified circuits responsible of decisions. It will enhance our comprehension of how these circuit dynamics respond to
variations and assessing their robustness.
Hence, these new inference methods will advance our understanding of how circuit structure affects how it generates behavior. Finally, it will also elucidate the mechanistic origins of the experimentally observed diversity in behavior sequences of genetically identical larvae.
This project seeks to achieve two prominent goals:
1) The design of inference methods specific to small neural circuits driving behavior. Our inference
methods will be directly applicable to analyze other neural circuits.
2) A framework for studying short-term effects of neurodegenerative diseases and their treatments. Because larva experiments can be generalized at a larger scale with the ability to identify and quantify alterations at the single-neuron level, they can be used as a proxy to study the degeneracy of neural circuits.
The Alzheimer Larva
Preliminary results by our team have already demonstrated the interest of focusing on decision circuits to study the effects of specific peptide mutations (Aβ1-40/42), known to be related to Alzheimer’s disease. In particular, it provides the opportunity to examine neural circuit-level changes in the early phases of Alzheimer’s or Parkinson’s disease, which is not accessible at such early stages and resolution in other models.
Hence, a robust inference method able to precisely locate and predict neural circuit alterations from
observed behavior would be a powerful tool to drive experimental investigations. Such algorithms
will open up a range of possibilities for examining the structure of the healthy circuit, as well as the
changes triggered by developmental abnormalities and disease. Furthermore, the fast reproducibility
rate of larva experiments will permit large-scale drug screens with my methodology providing a fast
and efficient tool for gauging the associated neural circuit changes. The project serves as
a basis for a full testing platform by linking observed behavior to neural distortion or recovery
