Raid AMPA receptor desensitization in catfish cone horizontal cells
ABSTRACT AMPA and NMDA type glutamate receptors were studied in isolated catfish cone horizontal cells using the whole-cell and outside-out patch-recording techniques. In whole-cell recordings, cyclothiazide (CTZ) enhanced the peak current in response to glutamate (in the presence of NMDA receptor antagonists). In patch recordings, currents evoked by rapid and maintained applications of glutamate desensitized with a time constant of one millisecond. CTZ blocked this rapid desensitization. Recovery from desensitization of the AMPA receptors was rapid, having a time constant of 8.65 ms. In contrast, the whole-cell and patch responses to applications of NMDA were much smaller than the AMPA receptor responses and did not desensitize. The relative contribution of these two receptor subtypes depends critically on the condition of the synapse; if glutamate levels are tonically present, the NMDA receptors contribute significantly to the postsynaptic response. If glutamate levels fall rapidly following the release of a single quantum of glutamate, then AMPA receptor currents will dominate the postsynaptic response.
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- "Functional CP-GluARs have been found in horizontal cells of every species investigated, including lizard (Jackman et al., 2011), fish (Eliasof and Jahr, 1997; Huang and Liang, 2005; Sun et al., 2010), skate (Kreitzer et al., 2009), and rabbit (Rivera et al., 2001; Figure 1B). Catfish cone horizontal cells, stellate neurons with enormous somata (Sakai and Naka, 1986), express extraordinarily fast CP-GluARs: in excised membrane patches at room temperature, glutamate-evoked currents desensitized with a time constant of ∼1 ms and recovered from desensitization with a time constant of less than 9 ms (Eliasof and Jahr, 1997). These rapid kinetics, rivaled only by GluARs receptors in avian auditory nuclei (Raman and Trussell, 1992), suggest that CP-GluARs may mediate local signaling in horizontal cell processes, because such brief conductances would be filtered strongly by the large membrane capacitance of the cell. "
ABSTRACT: The retina transforms light entering the eye into a sophisticated neural representation of our visual world. Specialized synapses, cells, and circuits in the retina have evolved to encode luminance, contrast, motion, and other complex visual features. Although a great deal has been learned about the cellular morphology and circuitry that underlies this image processing, many of the synapses in the retina remain incompletely understood. For example, excitatory synapses in the retina feature the full panoply of glutamate receptors, but in most cases specific roles for different receptor subtypes are unclear. In this brief review, I will discuss recent progress toward understanding how Ca(2+)-permeable AMPA receptors (CP-GluARs) contribute to synaptic transmission and newly discovered forms of synaptic plasticity in the retina.Frontiers in Molecular Neuroscience 09/2011; 4:27. DOI:10.3389/fnmol.2011.00027 · 4.08 Impact Factor
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- "AMPA receptors enter a desensitized state very rapidly (within several milliseconds) following application of glutamate (Kiskin et al., 1986; Patneau et al., 1993; Eliasof & Jahr, 1997). "
ABSTRACT: Glutamate is believed to be the primary excitatory neurotransmitter in the vertebrate retina, and its fast postsynaptic effects are elicited by activating NMDA-, kainate-, or AMPA-type glutamate receptors. We have characterized the ionotropic glutamate receptors present on retinal horizontal cells of the skate, which possess a unique all-rod retina simplifying synaptic circuitry within the outer plexiform layer (OPL). Isolated external horizontal cells were examined using whole-cell voltage-clamp techniques. Glutamate and its analogues kainate and AMPA, but not NMDA, elicited dose-dependent currents. The AMPA receptor antagonist GYKI 52466 at 100 microm abolished glutamate-elicited currents. Desensitization of glutamate currents was removed upon coapplication of cyclothiazide, known to potentiate AMPA receptor responses, but not by concanavalin A, which potentiates kainate receptor responses. The dose-response curve to glutamate was significantly broader in the presence of the desensitization inhibitor cyclothiazide. Polyclonal antibodies directed against AMPA receptor subunits revealed prominent labeling of isolated external horizontal cells with the GluR2/3 and GluR4 antibodies. 1-Naphthylacetyl spermine, known to block calcium-permeable AMPA receptors, significantly reduced glutamate-gated currents of horizontal cells. Downregulation of glutamate responses was induced by increasing extracellular ion concentrations of Zn2+ and H+. The present study suggests that Ca2+-permeable AMPA receptors likely play an important role in shaping the synaptic responses of skate horizontal cells and that alterations in extracellular concentrations of calcium, zinc, and hydrogen ions have the potential to regulate the strength of postsynaptic signals mediated by AMPA receptors within the OPL.Visual Neuroscience 09/2009; 26(4):375-87. DOI:10.1017/S0952523809990149 · 2.21 Impact Factor
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- "Another postsynaptic mechanism that might contribute to PPD is receptor desensitization (Zucker and Regehr, 2002). By using a caged glutamate compound, we showed that horizontal cell AMPA receptors remained only slightly desensitized 500 ms after an initial pulse of glutamate consistent with relatively rapid recovery of horizontal cell AMPA receptors from desensitization (Eliasof and Jahr, 1997). "
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.The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 04/2006; 26(9):2555-63. DOI:10.1523/JNEUROSCI.3667-05.2006 · 6.34 Impact Factor