Among the 4 Bordeaux Neurocampus teams selected by the FRM in 2016, 3 are from IINS:
Christophe Mulle team project:
Synaptic circuits of memory in physiological conditions and in Alzheimer’s disease
Synaptic plasticity is thought to underlie the initial encoding of memory. However, a precise identification of synaptic connections and circuits specifically targeted and modified by memory encoding is needed. This project deals with the CA3 region of the hippocampus which is involved in rapid, episodic memory formation, a form of memory greatly affected at the early stages of Alzheimer’s disease (AD). We propose to study mechanisms underlying the specification and plasticity of synaptic circuits in CA3 in physiological conditions, and in relation to AD. We will also examine the activity and plasticity of intact CA3 circuits in the mouse, in relation to episodic memory encoding. Finally, we will investigate what synaptic mechanisms are impacted in CA3 in mouse models of AD and how this could explain impairment of episodic memory.
Neural plasticity is a quintessential hallmark of the mammalian brain; it is critical for brain development, cognitive functions like learning and memory as well as brain diseases. Understanding the mechanisms of neural plasticity and its impact on brain function represents one of the most important challenges for neuroscience research. Enabled by the recent revolution of super-resolution microscopy, which is making it possible to visualize the dynamic inner life of neurons and synapses while they are embedded in their natural habitat of complex brain tissue, the project aims to uncover the anatomical determinants of neural function and plasticity. The project has the potential for groundbreaking discoveries that upend our understanding of neural plasticity and opens up new opportunities to study the pathophysiological mechanisms of brain disorders at an unprecedented spatial scale inside the living brain.
Contact Valentin Nägerl: tel 05 57 57 10 97 (P. 06 75 46 95 35) - website
Olivier Thoumine team project:
Investigation of neuroligin function in synapse assembly by optogenetic control of neuronal activity and signaling pathways
In this interdisciplinary project, we propose to investigate the signaling mechanisms associated with neurexin (NRX)/neuroligin (NLG) adhesion in synaptic differentiation, using novel single molecule detection and optogenetic approaches.
The main tasks are:
- Identifying the receptor tyrosine kinase (RTK) controlling NLG phosphorylation
- Single-molecule super-resolution imaging of NRX/NLG dynamics and nanoscale architecture in relation with scaffold proteins;
- Controlling NLG phosphorylation by repeated stimulation of light-gated RTKs;
- Investigating the functional impact of NLG phosphorylation on synaptic differentiation by electrophysiology, Behavioral characterization of knock-in mice expressing NLG phospho-mutants. We hope to make significant discoveries into the fundamental process of synaptogenesis and the regulation of the balance between excitatory and inhibitory synapses, a crucial parameter of brain function in physio-pathological situations including autism spectrum disorders.