title: A General Procedure to Study Subcellular Models of Transsynaptic Signaling at Inhibitory Synapses.
abstract: 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.
authors.affiliation: Institute of Biophysics, National Research Council Palermo, Italy.
authors.forename: Carmen A
authors.initials: CA
authors.lastname: Lupascu
authors.affiliation: European Brain Research Institute Rome, Italy.
authors.forename: Annunziato
authors.initials: A
authors.lastname: Morabito
authors.affiliation: European Brain Research Institute Rome, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Merenda
authors.affiliation: European Brain Research Institute Rome, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Marinelli
authors.affiliation: European Brain Research Institute Rome, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Marchetti
authors.affiliation: Institute of Biophysics, National Research Council Palermo, Italy.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Migliore
authors.affiliation: European Brain Research Institute Rome, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Cherubini
authors.affiliation: Institute of Biophysics, National Research Council Palermo, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Migliore
keywords: CA1 neurons; GABAergic synapses; Human Brain Project Collaboratory; NEURON simulator; Python; fitting procedure; gephyrin