Article

Synaptic Ca2+ in darkness is lower in rods than cones, causing slower tonic release of vesicles

Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.75). 06/2007; 27(19):5033-42. DOI: 10.1523/JNEUROSCI.5386-06.2007
Source: PubMed

ABSTRACT Rod and cone photoreceptors use specialized biochemistry to generate light responses that differ in their sensitivity and kinetics. However, it is unclear whether there are also synaptic differences that affect the transmission of visual information. Here, we report that in the dark, rods tonically release synaptic vesicles at a much slower rate than cones, as measured by the release of the fluorescent vesicle indicator FM1-43. To determine whether slower release results from a lower Ca2+ sensitivity or a lower dark concentration of Ca2+, we imaged fluorescent indicators of synaptic vesicle cycling and intraterminal Ca2+. We report that the Ca2+ sensitivity of release is indistinguishable in rods and cones, consistent with their possessing similar release machinery. However, the dark intraterminal Ca2+ concentration is lower in rods than in cones, as determined by two-photon Ca2+ imaging. The lower level of dark Ca2+ ensures that rods encode intensity with a slower vesicle release rate that is better matched to the lower information content of dim light.

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    • "Are there differences in adaptative signaling in cone and rod synapses and eventually also between the different active zones present in cone synapses? Recent Ca 2+ -imaging analyses strongly argue that this is the case (Johnson et al., 2007; Sheng et al., 2007). Most of our current knowledge about the physiology of retinal ribbon synapses was obtained from goldfish bipolar cells and salamander photoreceptors. "
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    ABSTRACT: Photoreceptors, the light-sensitive receptor neurons of the retina, receive and transmit a plethora of visual informations from the surrounding world. Photoreceptors capture light and convert this energy into electrical signals that are conveyed to the inner retina. For synaptic communication with the inner retina, photoreceptors make large active zones that are marked by synaptic ribbons. These unique synapses support continuous vesicle exocytosis that is modulated by light-induced, graded changes of membrane potential. Synaptic transmission can be adjusted in an activity-dependent manner, and at the synaptic ribbons, Ca(2+)- and cGMP-dependent processes appear to play a central role. EF-hand-containing proteins mediate many of these Ca(2+)- and cGMP-dependent functions. Since continuous signaling of photoreceptors appears to be prone to malfunction, disturbances of Ca(2+)- and cGMP-mediated signaling in photoreceptors can lead to visual defects, retinal degeneration (rd), and even blindness. This review summarizes aspects of signal transmission at the photoreceptor presynaptic terminals that involve EF-hand-containing Ca(2+)-binding proteins.
    Frontiers in Molecular Neuroscience 02/2012; 5:26. DOI:10.3389/fnmol.2012.00026 · 4.08 Impact Factor
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    • "The identity of the calcium sensor molecules that regulate exocytosis from photoreceptors is unclear. Experiments on nonmammalian rods and cones show that the sensor exhibits an unusually high affinity for Ca 2+ with a threshold of 400 nM and low cooperativity of approximately two Ca 2+ ions (Rieke & Schwartz, 1996; Thoreson et al., 2004; Sheng et al., 2007; Duncan et al., 2010). This is quite different from release at synapses employing synaptotagmin 1, which show a cooperativity of five Ca 2+ ions and a requirement for much higher Ca 2+ levels (Heidelberger et al., 1994; Bollmann et al., 2000; Schneggenburger & Neher, 2000; Beutner et al., 2001). "
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    ABSTRACT: Rod and cone photoreceptors possess ribbon synapses that assist in the transmission of graded light responses to second-order bipolar and horizontal cells of the vertebrate retina. Proper functioning of the synapse requires the juxtaposition of presynaptic release sites immediately adjacent to postsynaptic receptors. In this review, we focus on the synaptic, cytoskeletal, and extracellular matrix proteins that help to organize photoreceptor ribbon synapses in the outer plexiform layer. We examine the proteins that foster the clustering of release proteins, calcium channels, and synaptic vesicles in the presynaptic terminals of photoreceptors adjacent to their postsynaptic contacts. Although many proteins interact with one another in the presynaptic terminal and synaptic cleft, these protein-protein interactions do not create a static and immutable structure. Instead, photoreceptor ribbon synapses are remarkably dynamic, exhibiting structural changes on both rapid and slow time scales.
    Visual Neuroscience 11/2011; 28(6):453-71. DOI:10.1017/S0952523811000356 · 1.68 Impact Factor
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    • "retina; synaptic transmission; computer modeling; electrophysiology THE EXOCYTOSIS of synaptic vesicles is triggered by an elevation of intracellular Ca 2ϩ . The molecular machinery underlying exocytosis at the photoreceptor ribbon synapse has an unusually high affinity for Ca 2ϩ , requiring a Ca 2ϩ concentration in the 10 Ϫ7 –10 Ϫ6 M range (Duncan et al. 2010; Rieke and Schwartz 1996; Sheng et al. 2007; Thoreson et al. 2004) compared with the 10 Ϫ5 –10 Ϫ4 M range for most other synapses . (Beutner et al. 2001; Bollmann et al. 2000; Heidelberger et al. 1994; Schneggenburger and Neher 2000) The high Ca 2ϩ sensitivity in photoreceptors has led to the suggestion that the key Ca 2ϩ -dependent events controlling release might occur hundreds of nanometers from the mouth of voltage-gated Ca 2ϩ channels, where the local cytoplasmic Ca 2ϩ concentration is maximal. "
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    ABSTRACT: Light hyperpolarizes cone photoreceptors, causing synaptic voltage-gated Ca(2+) channels to open infrequently. To understand neurotransmission under these conditions, we determined the number of L-type Ca(2+) channel openings necessary for vesicle fusion at the cone ribbon synapse. Ca(2+) currents (I(Ca)) were activated in voltage-clamped cones, and excitatory postsynaptic currents (EPSCs) were recorded from horizontal cells in the salamander retina slice preparation. Ca(2+) channel number and single-channel current amplitude were calculated by mean-variance analysis of I(Ca). Two different comparisons-one comparing average numbers of release events to average I(Ca) amplitude and the other involving deconvolution of both EPSCs and simultaneously recorded cone I(Ca)-suggested that fewer than three Ca(2+) channel openings accompanied fusion of each vesicle at the peak of release during the first few milliseconds of stimulation. Opening fewer Ca(2+) channels did not enhance fusion efficiency, suggesting that few unnecessary channel openings occurred during strong depolarization. We simulated release at the cone synapse, using empirically determined synaptic dimensions, vesicle pool size, Ca(2+) dependence of release, Ca(2+) channel number, and Ca(2+) channel properties. The model replicated observations when a barrier was added to slow Ca(2+) diffusion. Consistent with the presence of a diffusion barrier, dialyzing cones with diffusible Ca(2+) buffers did not affect release efficiency. The tight clustering of Ca(2+) channels, along with a high-Ca(2+) affinity release mechanism and diffusion barrier, promotes a linear coupling between Ca(2+) influx and vesicle fusion. This may improve detection of small light decrements when cones are hyperpolarized by bright light.
    Journal of Neurophysiology 08/2011; 106(6):2922-35. DOI:10.1152/jn.00634.2011 · 3.04 Impact Factor
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