Objective Evidence has been emerging for astrocytes to play an important role in neuronal cooperation and information processing in the brain. Recent work has suggested that their activity may even regulate the shape of action potentials in the axon and thus the efficacy of synaptic transmission. However, the underlying physiological machinery remains poorly understood. We propose here that astrocytes play an active role in the analogue-digital regulation of presynaptic signalling. To decipher the role of astroglia in presynaptic signalling, in particular analogue-digital axonal information transfer, we focus on the giant mossy-fibre-CA3 synapse, well characterized in the host laboratory. Our working hypothesis is that astrocytes regulate spike generation and propagation in axons by modulating local extracellular potassium and possibly by releasing glutamate. To test this hypothesis, an innovative set of technique will be used: i) direct recordings of astrocytes and either presynaptic or postsynaptic elements of the synapse in the mossy-fibre to CA3 synapse; ii) genetic tools allowing specific targeting and stimulation of either astrocytes or neurons; iii) pioneering imaging tools, such as FLIM, to directly measure the calcium entry and glutamate-sensing fluorescent reporter to reveal glutamate release by the astrocytes. The proposed project should unravel the mechanisms by which astrocytes control axonal information transfer in neural networks axonal excitability while shedding light on poorly understood features of astrocyte physiology. Fields of science natural sciencesbiological sciencesneurobiologycognitive neurosciencenatural scienceschemical sciencesinorganic chemistryalkali metalsnatural scienceschemical sciencesinorganic chemistryalkaline earth metalsnatural sciencescomputer and information sciencesdata sciencedata processingnatural sciencescomputer and information sciencesartificial intelligencecomputational intelligence Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Topic(s) MSCA-IF-2016 - Individual Fellowships Call for proposal H2020-MSCA-IF-2016 See other projects for this call Funding Scheme MSCA-IF-EF-ST - Standard EF Coordinator UNIVERSITY COLLEGE LONDON Net EU contribution € 195 454,80 Address GOWER STREET WC1E 6BT London United Kingdom See on map Region London Inner London — West Camden and City of London Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 195 454,80