Summary
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. This synapse is accessible
to presynaptic recording, due to its large size, 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 have been generated. However, even basic properties
of 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 subcellular
level, we want to elucidate the biophysical mechanisms of transmission and synaptic plasticity in the
same depth as previously achieved at peripheral and brainstem synapses, classical synaptic models. At the
network 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 and
structural approaches. For the analysis of synaptic transmission and plasticity, we will combine direct preand
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 research, the hippocampal mossy fiber synapse could become the first synapse
in the history of neuroscience in which we reach 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, or connectivity are impaired.
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. This synapse is accessible
to presynaptic recording, due to its large size, 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 have been generated. However, even basic properties
of 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 subcellular
level, we want to elucidate the biophysical mechanisms of transmission and synaptic plasticity in the
same depth as previously achieved at peripheral and brainstem synapses, classical synaptic models. At the
network 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 and
structural approaches. For the analysis of synaptic transmission and plasticity, we will combine direct preand
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 research, the hippocampal mossy fiber synapse could become the first synapse
in the history of neuroscience in which we reach 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, or connectivity are impaired.
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More information & hyperlinks
| Web resources: | https://cordis.europa.eu/project/id/692692 |
| Start date: | 01-03-2017 |
| End date: | 31-08-2022 |
| Total budget - Public funding: | 2 677 500,00 Euro - 2 677 500,00 Euro |
Cordis data
Original 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 cells
and dendrites of CA3 pyramidal neurons, is the ideal synapse to address this question. This synapse is accessible
to presynaptic recording, due to its large size, 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 have been generated. However, even basic properties
of 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 subcellular
level, we want to elucidate the biophysical mechanisms of transmission and synaptic plasticity in the
same depth as previously achieved at peripheral and brainstem synapses, classical synaptic models. At the
network 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 and
structural approaches. For the analysis of synaptic transmission and plasticity, we will combine direct preand
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 research, the hippocampal mossy fiber synapse could become the first synapse
in the history of neuroscience in which we reach 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, or connectivity are impaired.
Status
CLOSEDCall topic
ERC-ADG-2015Update Date
27-04-2024
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