A General Procedure to Study Subcellular Models of Transsynaptic Signaling at Inhibitory Synapses

Computational modeling of brain circuits requires the definition of many parameters that are difficult to determine from experimental findings. One way to help interpret these data is to fit them using a particular kinetic model. In this paper, we propose a general procedure to fit individual synapt...

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Bibliographic Details
Published in:Frontiers in neuroinformatics 2016-06, Vol.10, p.23-23
Main Authors: Lupascu, Carmen A, Morabito, Annunziato, Merenda, Elisabetta, Marinelli, Silvia, Marchetti, Cristina, Migliore, Rosanna, Cherubini, Enrico, Migliore, Michele
Format: Article
Language:English
Subjects:
Animals
Brain research
Computational neuroscience
Experiments
Gephyrin
Hippocampus
Neurons
Neuroscience
Neurosciences
Optimization techniques
Proteins
Pyramidal cells
Synaptic transmission
γ-Aminobutyric acid
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Summary:Computational modeling of brain circuits requires the definition of many parameters that are difficult to determine from experimental findings. One way to help interpret these data is to fit them using a particular kinetic model. In this paper, we propose a general procedure to fit individual synaptic events recorded from voltage clamp experiments. Starting from any given model description (mod file) in the NEURON simulation environment, the procedure exploits user-defined constraints, dependencies, and rules for the parameters of the model to fit the time course of individual spontaneous synaptic events that are recorded experimentally. The procedure, implemented in NEURON, is currently available in ModelDB. A Python version is installed, and will be soon available for public use, as a standalone task in the Collaboratory Portal of the Human Brain Project. To illustrate the potential application of the procedure, we tested its use with various sets of experimental data on GABAergic synapses; gephyrin and gephyrin-dependent pathways were chosen as a suitable example of a kinetic model of synaptic transmission. For individual spontaneous inhibitory events in hippocampal pyramidal CA1 neurons, we found that gephyrin-dependent subcellular pathways may shape synaptic events at different levels, and can be correlated with cell- or event-specific activity history and/or pathological conditions.
ISSN:1662-5196
1662-5196
DOI:10.3389/fninf.2016.00023