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J. Gottesman, M.A. Sikora, R.F. Miller; Computational Modeling of the Ribbon Synapse . Invest. Ophthalmol. Vis. Sci. 2005;46(13):4543.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To create a computational model of the ribbon synapse for use in testing hypotheses of synaptic communication in the outer and inner plexiform layers. Methods: A model of the ribbon synapse was developed in NEURON to replicate both pre– and postsynaptic functions of this glutamatergic juncture. The presynaptic portion of the model is rich in anatomical and physiological detail and includes multiple release sites for each ribbon based on ultrastructural studies of presynaptic terminals, presynaptic voltage at the terminal, the activation of voltage–gated calcium channels and a calcium–dependent release mechanism whose rate varies as a function of the calcium concentration monitored at two different sites which control both an ultrafast pool of docked vesicles and a slower, release ready pool of tethered vesicles. The postsynaptic portion of the program models diffusion of glutamate and the physiological properties of glutamatergic neurotransmission in target cells. Results: We demonstrate the behavior of the model using the retinal bipolar cell to ganglion cell ribbon synapse. The model was constrained by the anatomy of salamander bipolar terminals based on the ultrastructure of these synapses and presynaptic contacts were placed onto realistic ganglion cell morphology activated by a range of ribbon synapses (46–138). Presynaptic release in the model replicates physiological data from goldfish M1b bipolar terminals for release evoked by flash photolysis of caged calcium or membrane depolarization. The model demonstrates paired pulse depression as observed for the goldfish terminals. We used model parameters that produced those presynaptic release behaviors as inputs to a compartmental model built from reconstruction of an HRP–injected ganglion cell. These inputs could excite the ganglion cell in a manner consistent with physiological observations. Modifications of the model to replicate vesicular release evoked by flash photolysis of caged calcium in salamander photoreceptors are also considered. Conclusions: This model is a comprehensive, first generation attempt to assemble our present understanding of the ribbon synapse into a domain that permits testing our understanding of this important structure. We believe that with minor modifications of this model it can be fine tuned for other ribbons synapses.
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