Report

Teaser, summary, work performed and final results

Periodic Reporting for period 2 - C.NAPSE (TOWARDS A COMPREHENSIVE ANALYSIS OF EXTRACELLULAR SCAFFOLDING AT THE SYNAPSE)

Teaser

Chemical synapses are the specialized structures supporting communication between neurons in the brain and between neurons and muscles at neuromuscular junctions. They represent the elementary structures processing information transfer within neuronal networks and they rely on...

Summary

Chemical synapses are the specialized structures supporting communication between neurons in the brain and between neurons and muscles at neuromuscular junctions. They represent the elementary structures processing information transfer within neuronal networks and they rely on a precise molecular organization that was selected early during evolution.

The human brain might contain up to a million of billion synapses, which represents an ultimate challenge for precise characterization of these structures at the molecular scale. To reduce complexity, the current project uses the nematode C. elegans, a simple model organism that contains less than ten thousand synapses. Yet, C. elegans synapses are very similar to human synapses at the molecular level. This project takes advantage of powerful genetic strategies in combination with cutting-edge in vivo imaging and electrophysiology tools to identify new molecules and new mechanisms involved in synaptic formation and function.

This project will increase our fundamental knowledge of the synapse and will shed light on the physiopathology of several neuropsychiatric illnesses in which synaptic defects are at the core of the disease.

Work performed

Since the beginning of this project, our team has conducted several genetic screens based on the visualization of synaptic proteins in living worms and identified several new genes required for the formation and stability of chemical synapses. We identified novel synaptic proteins that are critical to recruit neurotransmitter receptors at synapses and to maintain synaptic function. We are currently implementing novel microscopy tools in order to analyse the molecular organization of synapses in vivo. In addition, we are currently investigating the impact of aging on the neuromuscular system and we are conducting genetic screens to identify new modulators of neuromuscular aging.

Final results

The nematode C. elegans provides a unique means to identify critical components of synaptic organization using powerful unbiased genetics. It should lead to the identification of novel genes required for neuro-neuronal communication and possibly shed light on molecular dysfunctions at the basis of neuropsychiatric diseases.

In the future, the nematode C. elegans might represent a powerful system for the characterization of genetic variations identified by genome sequencing of patients suffering neuropsychiatric diseases and for which the biological significance is extremely difficult to ascertain in the absence of functional tests.