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<h2020:692692>
Biophysics and circuit function of a giant cortical glutamatergic synapse

Description

A fundamental question in neuroscience is how the biophysical properties of synapses shape higher networkcomputations. The hippocampal mossy fiber synapse, formed between axons of dentate gyrus granule cellsand dendrites of CA3 pyramidal neurons, is the ideal synapse to address this question. This synapse is accessibleto presynaptic recording, due to its large size, allowing a rigorous investigation of the biophysicalmechanisms of transmission and plasticity. Furthermore, this synapse is placed in the center of a memorycircuit, and several hypotheses about its network function have been generated. However, even basic propertiesof this key communication element remain enigmatic. The ambitious goal of the current proposal, GIANTSYN,is to understand the hippocampal mossy fiber synapse at all levels of complexity. At the subcellularlevel, we want to elucidate the biophysical mechanisms of transmission and synaptic plasticity in thesame depth as previously achieved at peripheral and brainstem synapses, classical synaptic models. At thenetwork level, we want to unravel the connectivity rules and the in vivo network function of this synapse,particularly its role in learning and memory. To reach these objectives, we will combine functional andstructural approaches. For the analysis of synaptic transmission and plasticity, we will combine direct preandpostsynaptic patch-clamp recording and high-pressure freezing electron microscopy. For the analysis ofconnectivity and network function, we will use transsynaptic labeling and in vivo electrophysiology. Basedon the proposed interdisciplinary research, the hippocampal mossy fiber synapse could become the first synapsein the history of neuroscience in which we reach complete insight into both synaptic biophysics andnetwork function. In the long run, the results may open new perspectives for the diagnosis and treatment ofbrain diseases in which mossy fiber transmission, plasticity, or connectivity are impaired.

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