A model of the ribbon synapse was developed 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 anatomical 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 that is monitored at two different sites which control both an ultrafast, docked pool of vesicles and a 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. 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). These inputs could excite the cell in a manner consistent with physiological observations. 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 ribbon synapses.
Bibliographical noteFunding Information:
Supported by NEI grant # R01-12833 to R.F.M. and J.G. We thank Josh Mrazek for help in running simulations and writing custom Perl scripts. We thank Derek Miller and Terry Wu for help with figure preparation. Drs. Jurgen Fohlmeister, Pratip Mitra and Wallace Thoreson provided helpful comments on the manuscript. We thank Drs. Michael Hines and Joel Stiles and Tom Bartol for their support for the programs NEURON and MCell, respectively. MCell simulations were carried out using computing resources at the University of Minnesota Supercomputing Institute.
- Exocytotic mechanism
- Release site vesicle pool
- Ribbon synapse
- Ultrafast pool