Biophysics and circuit function of a giant cortical glutamatergic synapse

A fundamental question in neuroscience is how the biophysical properties of synapses shape higher network computations. The hippocampal mossy fiber synapse, formed between axons of dentate gyrus granule cells and dendrites of CA3 pyramidal neurons, is the ideal synapse to address this question. Due to the large size, this synapse is accessible to presynaptic recording, allowing a rigorous investigation of the biophysical mechanisms of transmission and plasticity. Furthermore, this synapse is placed in the center of a memory circuit, and several hypotheses about its network function are available. However, even basic properties of this synapse 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 subcellular level, we want to understand the biophysical mechanisms of transmission and synaptic plasticity in the same depth as previously achieved at the calyx of Held, a classical synaptic model. At the network level, we want to unravel the con-nectivity 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 and structural approaches. For the analysis of synaptic transmission and plasticity, we will combine direct pre- and postsynaptic patch-clamp recording and high-pressure freezing electron microscopy. For the analysis of connectivity and network function, we will use transsynaptic labeling and in vivo electrophysiology. Based on the proposed interdisciplinary re-search, the hippocampal mossy fiber synapse could become the first synapse in the history of neuroscience in which we have complete insight into both synaptic biophysics and network function. In the long run, the results may open new perspectives for the diagnosis and treatment of brain diseases in which mossy fiber transmission, plasticity, and connectivity are impaired.

Project reference: 692692


Contract type: ERC Advanced Grant

EU contribution: EUR 2.677.500

Project programme: Horizon 2020 (EU Framework Programme for Research and Innovation)

Principal Investigator: Prof. Peter Jonas

Team members:

Florian Marr (Senior Lab Technician)

Magdalena Picher (Postdoc)

Alois Schlögl (Software Engineer)

David Vandael (Postdoc)

Xiaomin Zhang (Postdoc)