Summary

Synapses are the central information processors in the brain. Their function, efficacy and plasticity are key determinants of all brain functions, and of the corresponding behavioral output. Conversely, aberrant synapse function is the cause of many neurological and psychiatric disorders. Our ultimate objective is to generate a functional virtual synapse, in silico, that covers both the presynaptic and postsynaptic compartments.

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RESEARCH INFRASTRUCTURE

This CRC 1286 builds on extensive infrastructure that has been built over the last decade by many institutions,...

DETAILS

... ranging from the Excellence Initiative to measures promoted by the German Research Foundation (DFG), the German Ministry for Education and Research (BMBF), the Max Planck Society, and the State of Lower Saxony.

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TEAM MEMBERS

Our Team consists of 27 principal investigators and one worker of coordination.

DETAILS

They are Scientists of different institutions in the region of Göttingen and join forces with each other for research purposes.

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PROJECTS

The CRC 1286 works interdisciplinary (see research Infrastructure). It is divided into 3 research areas.

DETAILS

Project area A – C, one associated and three central projetcs support our research to take some more steps towards future.

Progress of research

Synapses are the central information processors in the brain. Their function, efficacy and plasticity are key determinants of all brain functions, and of the corresponding behavioral output. Conversely, aberrant synapse function is the cause of many neurological and psychiatric disorders. Our ultimate objective is to generate a functional virtual synapse, in silico, that covers both the presynaptic and postsynaptic compartments.
Over the first funding period we proposed to obtain a wide set of molecular, structural and functional data on a prototypic, averaged model synapse, while only engaging a few computational projects. For the second funding period we envisioned refining these data by further wet-lab experimental work, while at the same time enhancing strongly the computational aspects, by recruiting new computational neuroscience projects into the CRC. Finally, the work will culminate in the third funding period, in which we will rely even more heavily on in silico modelling.
We followed this plan closely during the first funding period, and we are “on schedule” with regard to most aspects. We determined the locations of many synaptic organelles and proteins, their copy numbers, their movement rates, their metabolic turnover, several of their post-translational modifications, and their interactomes. We also performed multiple analyses of neuronal and synaptic RNAs and lipids. Finally, we initialized several modeling projects, in which collaborations with experimentalists were employed to provide an understanding of defined synaptic processes.
During the second funding period, we will continue our work along these lines, while strongly enhancing the computational aspects. As we proposed in 2017, we more than doubled the number of computational projects, which now address multiple aspects of synaptic transmission, from protein movement and nanoscale organization to long-term dynamics and plasticity. The completion of these projects will place us in an optimal position to establish synapse function models in the third funding period.
Our synaptic models will be used to answer questions on synaptic function and dysfunction, and will be extremely important in the context of connectomics efforts, since they will suggest the functional responses of synapses in given connectomes, thereby greatly increasing the functionality of structural connectomes.

3D Model of a Synapse

The movie displays a rotating example of a rat neuronal synapse with differing sets of protein types.
The synaptic membrane types comprise the plasma membrane, 375 vesicles, 7 endosomes and one mitochondrion.
They were modeled from membrane coordinates of several layers. The number and location of 62 different protein types were analyzed so that they could be placed accordingly inside the synaptic cytosol and on the synaptic membranes. In total, the protein count reaches 300,000.

THE NANOSCALE DYNAMICS OF PROTEINS IN THE SYNAPTIC BOUTON

Eine Standbildansicht der Proteinbewegung neben dem synaptischen A still view of the protein motion next to the synaptic vesicle cluster. Each molecule is color-coded according to its diffusion coefficient in the place of its current location. Darker violet colors indicate lower diffusion coefficients.

A view of soluble protein movement in the synapse. Only synaptic vesicles (grey shapes) and soluble proteins are shown, the plasma membrane surrounding the synapse is transparent. Each colored shape is a single protein molecule, with the molecules of the same protein type having the same color and shape.

laboratory of Prof. Silvio Rizzoli

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