Project description
Research explores how special neuron parts affect brain activity and lead to neurological diseases
Neurons have the remarkable ability to process information while maintaining their activity stable. A special part of neurons – axon initial segment (AIS) – plays a key role in managing the messages neurons send. Contrary to common perception that the AIS is a static and passive structure, recent discoveries reveal it can adapt, causing long-lasting changes in neuron excitability. The ERC-funded PLaisTICITY project seeks to understand how the AIS adapts to changes in neuronal activity and its role in diseases like Angelman syndrome. Using cutting-edge tools such as genome editing, proteomics, optogenetics and electrophysiology, the proposed research aims to explore how AIS plasticity affects neuron function and identify how maladaptations might contribute to neurological diseases.
Objective
Neurons have the remarkable ability to continuously integrate and propagate information while maintaining their activity state within physiological range. The axon initial segment (AIS) is the keystone of neuronal excitability and pivotal for the maintenance of network homeostasis.
The molecular organization of the AIS dictates the generation of action potentials, and thereby shapes the principal output of neurons. Although the AIS has long been considered as a static and passive structure, recent work from my lab and others demonstrated that network activity induces robust plasticity of the AIS, causing long-lasting changes in excitability. However, how AIS plasticity is regulated to maintain network homeostasis remains elusive.
In this proposal, I aim to resolve, at the molecular level, how the AIS adapts in response to acute and chronic changes in neuronal activity and how maladaptation may lead to disease. To this end, I developed genome editing tools to label and manipulate endogenous AIS components, enabling live and super-resolution imaging of AIS organization. In combination with proteomics, optogenetics and electrophysiology, this project will address the following key objectives:
1. Resolve the nanoscale distribution and dynamics of AIS components
2. Unravel the mechanisms controlling acute and chronic re-distribution of ion channels during AIS plasticity and their consequences for excitability
3. Address the implication of maladaptive AIS plasticity in the pathology of Angelman Syndrome
This project bridges the cell biology of the neuron to its physiology, provides new insights into how AIS plasticity orchestrates network activity and identifies how maladaptation contributes to disease.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
- natural sciencesbiological sciencesneurobiology
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsproteomics
- natural sciencesphysical sciencesopticsmicroscopysuper resolution microscopy
- medical and health sciencesbasic medicinepathology
- medical and health sciencesbasic medicinephysiologyhomeostasis
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Keywords
Programme(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Topic(s)
Funding Scheme
HORIZON-ERC - HORIZON ERC GrantsHost institution
1081 HV Amsterdam
Netherlands