Neural coding with the tripartite synapse. (360G-Wellcome-101896_Z_13_Z)

In our quest to decipher the brain circuit machinery astroglia have emerged as an important third participant of the signal exchange between pre- and postsynaptic neurons. To understand principles of information processing in such tripartite circuits represents a conceptual challenge. How the multiple modalities of intracellular astrocyte signalling translate into meaningful communication with neurons remains poorly understood. Our long-term aim is therefore to understand how generation, pr opagation and storage of informative signals in tripartite brain circuits form memories and shape a physiological response, in health and disease. We will take full advantage of the on-going methodological revolution in sub-cellular real-time imaging, coupled with pharmaco- and optogenetic approaches ex-vivo and in-vivo and aided by biophysical and neural-network modelling. The five-year strategy will build upon our recent discoveries which have unveiled novel principles of synaptic organisat ion and plasticity including the regulatory role of astrocytic signalling. Firstly, we will employ our novel FLIM-based Ca2+ imaging technique to decipher the code of causalities arising between the synaptic identity and Ca2+ homeostasis machineries at tripartite connections. Secondly, we will establish how the diverse neural signals are integrated and possibly stored by non-excitable astroglia operating their Ca2+-wave communication medium. Thirdly, we will explore and expand the classical rule s of synaptic plasticity to meta-plasticity of the tripartite synapse. Fourthly, we will establish how the operational assemblies of nerve and glial cells interact to support a physiological function. Finally, we will attempt to formulate how astroglial signalling impinges on functional modalities of theoretical neural networks.