title: Modeling and measurement of vesicle pools at the cone ribbon synapse: Changes in release probability are solely responsible for voltage-dependent changes in release.
abstract: Postsynaptic responses are a product of quantal amplitude (Q), size of the releasable vesicle pool (N), and release probability (P). Voltage-dependent changes in presynaptic Ca(2+) entry alter postsynaptic responses primarily by changing P but have also been shown to influence N. With simultaneous whole cell recordings from cone photoreceptors and horizontal cells in tiger salamander retinal slices, we measured N and P at cone ribbon synapses by using a train of depolarizing pulses to stimulate release and deplete the pool. We developed an analytical model that calculates the total pool size contributing to release under different stimulus conditions by taking into account the prior history of release and empirically determined properties of replenishment. The model provided a formula that calculates vesicle pool size from measurements of the initial postsynaptic response and limiting rate of release evoked by a train of pulses, the fraction of release sites available for replenishment, and the time constant for replenishment. Results of the model showed that weak and strong depolarizing stimuli evoked release with differing probabilities but the same size vesicle pool. Enhancing intraterminal Ca(2+) spread by lowering Ca(2+) buffering or applying BayK8644 did not increase PSCs evoked with strong test steps, showing there is a fixed upper limit to pool size. Together, these results suggest that light-evoked changes in cone membrane potential alter synaptic release solely by changing release probability.
authors.affiliation: Truhlsen Eye Institute, Department of Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha, Nebraska.|Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, Nebraska.
authors.forename: Wallace B
authors.initials: WB
authors.lastname: Thoreson
authors.affiliation: Truhlsen Eye Institute, Department of Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha, Nebraska.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Van Hook
authors.affiliation: Department of Mathematics, University of Nebraska, Lincoln, Nebraska.
authors.forename: Caitlyn
authors.initials: C
authors.lastname: Parmelee
authors.affiliation: Department of Mathematics, University of Nebraska, Lincoln, Nebraska.|Department of Mathematics, Pennsylvania State University, State College, Pennsylvania.
authors.forename: Carina
authors.initials: C
authors.lastname: Curto
mesh_terms: D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000557:Ambystoma; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002120:Calcium Channel Agonists / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism; D005260:Female; D007700:Kinetics; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology*; D008959:Models, Neurological; D018408:Patch-Clamp Techniques; D011336:Probability; D012160:Retina / Q000187:drug effects / Q000502:physiology*; D017949:Retinal Cone Photoreceptor Cells / Q000187:drug effects / Q000502:physiology*; D051248:Retinal Horizontal Cells / Q000187:drug effects / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D013572:Synaptic Vesicles / Q000187:drug effects / Q000378:metabolism*; D046509:Tissue Culture Techniques
chemical_list: D002120:Calcium Channel Agonists; D015220:Calcium Channels; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D002118:Calcium
keywords: cone photoreceptor; modeling; ribbon synapse; vesicle pools