Molecular and cellular investigation of neuron-astroglia interactions: Understanding brain function and dysfunction
Coordinator: Christian STEINHÄUSER
Project Number: 202167
EC contribution: € 2,988,450.00
Project website: http://www.neuroglia.eu/welcome.php
Astroglial cells are now recognized as active elements in the brain that sense and integrate synaptic signals and, by releasing gliotransmitters, regulate synaptic efficacy and cerebral blood flow. Despite accrued knowledge, many fundamental aspects of neuron-astroglia partnerships remain open, or have been poorly addressed in a functional context in vivo. For example, does astroglia heterogeneity reflect distinct functions? How do astroglial and neuronal networks interact locally and temporally? How does disruption of neuron-glia interactions contribute to brain disorders? Leading European research groups in the field have gathered in NeuroGLIA to address such questions using a multi-disciplinary approach, including transgenic astroglia-subtype specific mice, electrophysiology and high resolution laser scanning microscopy in vitro and in vivo (including awake mice). This will enable the consortium:
- to verify the potential of activated astroglia to signal back to neurons rapidly;
- to define the spatial-temporal dynamics of neuron–astroglia reciprocal signalling;
- to clarify the specific function of different astroglial subtypes in modulation of neuronal excitability and transmission, and in the control of neurovascular coupling.
NeuroGLIA will also investigate how dysfunction of neuron-astroglia signalling contributes to the pathogenesis of brain disorders, focussing on epilepsy. In animal models of epilepsy, astroglial activity will be analyzed with respect to initiation, maintenance and cessation of epileptiform activity, also in relation to blood flow changes and activation of inflammatory pathways. Importantly, access to living tissue from epilepsy patients, allows NeuroGLIA to investigate neuron-astroglia interactions and its dysregulation in the human brain. NeuroGLIA is thus in the privileged position to unravel fundamental mechanisms of neuron-astroglia signalling in health and disease, opening new perspectives for specific therapeutic strategies.