title: Paired-pulse depression at photoreceptor synapses.
abstract: Synaptic depression produced by repetitive stimulation is likely to be particularly important in shaping responses of second-order retinal neurons at the tonically active photoreceptor synapse. We analyzed the time course and mechanisms of synaptic depression at rod and cone synapses using paired-pulse protocols involving two complementary measurements of exocytosis: (1) paired whole-cell recordings of the postsynaptic current (PSC) in second-order retinal neurons and (2) capacitance measurements of vesicular membrane fusion in rods and cones. PSCs in ON bipolar, OFF bipolar, and horizontal cells evoked by stimulation of either rods or cones recovered from paired-pulse depression (PPD) at rates similar to the recovery of exocytotic capacitance changes in rods and cones. Correlation between presynaptic and postsynaptic measures of recovery from PPD suggests that 80-90% of the depression at these synapses is presynaptic in origin. Consistent with a predominantly presynaptic mechanism, inhibiting desensitization of postsynaptic glutamate receptors had little effect on PPD. The depression of exocytotic capacitance changes exceeded depression of the presynaptic calcium current, suggesting that it is primarily caused by a depletion of synaptic vesicles. In support of this idea, limiting Ca2+ influx by using weaker depolarizing stimuli promoted faster recovery from PPD. Although cones exhibit much faster exocytotic kinetics than rods, exocytotic capacitance changes recovered from PPD at similar rates in both cell types. Thus, depression of release is not likely to contribute to differences in the kinetics of transmission from rods and cones.
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha, Nebraska 68198-5840, USA.
authors.forename: Katalin
authors.initials: K
authors.lastname: Rabl
authors.forename: Lucia
authors.initials: L
authors.lastname: Cadetti
authors.forename: Wallace B
authors.initials: WB
authors.lastname: Thoreson
mesh_terms: D000818:Animals; D001581:Benzothiadiazines / Q000494:pharmacology; D004307:Dose-Response Relationship, Radiation; D025802:Electric Capacitance; D004558:Electric Stimulation; D005089:Exocytosis / Q000187:drug effects / Q000502:physiology; D005971:Glutamates / Q000494:pharmacology; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D009433:Neural Inhibition / Q000528:radiation effects*; D018408:Patch-Clamp Techniques / Q000379:methods; D010786:Photoreceptor Cells / Q000502:physiology* / Q000528:radiation effects; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D017949:Retinal Cone Photoreceptor Cells / Q000502:physiology / Q000528:radiation effects; D017948:Retinal Rod Photoreceptor Cells / Q000502:physiology / Q000528:radiation effects; D013569:Synapses / Q000502:physiology* / Q000528:radiation effects; D013997:Time Factors; D014562:Caudata; D014795:Visual Pathways / Q000502:physiology / Q000528:radiation effects
chemical_list: C440256:4-methoxy-7-nitroindolinyl-glutamate; D001581:Benzothiadiazines; D005971:Glutamates; D007211:Indoles; C004639:cyclothiazide