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Signal Formation in Synaptic Circuits with Astroglia

Final Report Summary - NETSIGNAL (Signal Formation in Synaptic Circuits with Astroglia)

In the past decade, astroglia have emerged as an active and critical partner in neural circuit communication in the brain, in health and disease. However, the increasing variety of mechanisms which reportedly contribute to astroglia-neuron signal exchange is at a conceptual bottleneck. How these multiple and diverse mechanisms relate to the functional organisation of astroglia, whether this relationship persists or whether it adapts to neural activity remains poorly understood. Our overall objective was to establish principles that guide signal formation, integration and propagation in neural circuits interacting with astroglia. Over the course of this project we successfully set up all major cutting-edge techniques designated as per the planned research strategy. These include two-photon excitation imaging, in brain slices and in intact animals, combined with single-cell electrophysiology; time-resolved fluorescence imaging; high-level network models incorporating glial cells; viral transduction of genetic optical sensor transduction, and super-resolution methods. Equipped with these approaches, we have established a relationship between synaptic identity and local glial coverage, discovered important roles the glial transporter of inhibitory neurotransmitter GABA in controlling synaptic circuits, identified an axonal plasticity mechanism underlying classical neuronal adaptation, unveiled information-rich landscapes of calcium in neural and astroglial assemblies, and established a novel, high-end biophysical framework for testing physiological hypotheses pertinent to astroglial function. The methods established and the results obtained yield some conceptual insights into the basic machinery underpinning the activity of brain circuits with astroglia. The scientific results arising from the present project have been published in >35 research papers and reviews including leading journals (Nat Neurosci, Neuron, Nat Commun, Nat Protocols, Nat Chem Biol, PNAS USA, Cell Reports, Nat Rev Neurosci, Trends Neurosci, etc.), and reported orally at >60 international scientific conferences, workshops, and institutional seminars.