The Nature of Surround-Induced Depolarizing Responses in Goldfish Cones

Abstract

Cones in the vertebrate retina project to horizontal and bipolar cells and the horizontal cells feedback negatively to cones. This organization forms the basis for the center/surround organization of the bipolar cells, a fundamental step in the visual signal processing. Although the surround responses of bipolar cells have been recorded on many occasions, surprisingly, the underlying surround-induced responses in cones are not easily detected. In this paper, the nature of the surround-induced responses in cones is studied. Horizontal cells feed back to cones by shifting the activation function of the calcium current in cones to more negative potentials. This shift increases the calcium influx, which increases the neurotransmitter release of the cone. In this paper, we will show that under certain conditions, in addition to this increase of neurotransmitter release, a calcium-dependent chloride current will be activated, which polarizes the cone membrane potential. The question is, whether the modulation of the calcium current or the polarization of the cone membrane potential is the major determinant for feedback-mediated responses in second-order neurons. Depolarizing light responses of biphasic horizontal cells are generated by feedback from monophasic horizontal cells to cones. It was found that niflumic acid blocks the feedback-induced depolarizing responses in cones, while the shift of the calcium current activation function and the depolarizing biphasic horizontal cell responses remain intact. This shows that horizontal cells can feed back to cones, without inducing major changes in the cone membrane potential. This makes the feedback synapse from horizontal cells to cones a unique synapse. Polarization of the presynaptic (horizontal) cell leads to calcium influx in the postsynaptic cell (cone), but due to the combined activity of the calcium current and the calcium-dependent chloride current, the membrane potential of the postsynaptic cell will be hardly modulated, whereas the output of the postsynaptic cell will be strongly modulated. Since no polarization of the postsynaptic cell is needed for these feedback-mediated responses, this mechanism of synaptic transmission can modulate the neurotransmitter release in single synaptic terminals without affecting the membrane potential of the entire cell.

Synaptic transmission at retinal ribbon synapses

“…In support of such a feedback relationship between I Ca and I Cl(Ca) (Thoreson et al, 2003a). In cones, E Cl appears to be near or slightly below the dark resting potential (Kaneko and Tachibana, 1986;Thoreson and Burkhardt, 1991;Kraaij et al, 2000;Thoreson and Bryson, 2005), whereas in rods it is 25 mV positive to the dark resting potential . When E Cl is negative, activation of I Cl(Ca) is expected to enhance I Ca via direct actions of Cl − but to inhibit I Ca via membrane hyperpolarization.…”

“…Kamermans and his co-workers (Verweij et al, 1996;Kraaij et al, 2000;Kamermans et al, 2001; reviewed in Kamermans and Fahrenfort, 2004) have elaborated a hypothesis whereby feedback shifts the operating range of the I Ca in cones. In the goldfish retina, illuminating the cone with a surround displaced the Ca-activation curve to the left by about −7.5 mV.…”

“…E Cl in cones appears to be near or slightly negative to the dark resting potential (Kaneko and Tachibana, 1986;Thoreson and Burkhardt, 1991;Kraaij et al, 2000;Thoreson and Bryson, 2005) but in the presence of background illumination, the cone membrane potential often passes below E Cl . Blocking I Cl(Ca) with niflumic acid blocks feedback depolarization in goldfish cones, but fails to block depolarizing responses in biphasic horizontal cells that are thought to arise from horizontal cell to cone feedback (Kraaij et al, 2000). These data are interpreted as suggesting that post-receptoral consequences of feedback are potently influenced by feedback-induced shifts in I Ca but only weakly influenced by feedback depolarization per se.…”

The dynamic characteristics of the feedback signal from horizontal cells to cones in the goldfish retina

“…This induces a small inward current ( Fig. 2A) with a time constant of about 90 ms, which has been identified as an increased Ca 2+ current (Verweij et al 1996;Kraaij et al 2000a). The mean time constant of this response was 87 ± 4 ms (n = 18).…”

Effects of pH Buffering on Horizontal and Ganglion Cell Light Responses in Primate Retina: Evidence for the Proton Hypothesis of Surround Formation

“…Despite considerable study, the synaptic mechanism that mediates this feedback has been difficult to identify and remains controversial. Early experiments in non-mammalian retina suggested that horizontal cell feedback to cones was mediated by a GABAergic synapse, but more recent experiments show that feedback is not affected by pharmacological manipulation of GABAergic neurotransmission (Thoreson and Burkhardt, 1990;Verweij et al, 1996;Vessey et al, 2005) and that horizontal cell feedback operates via a nonvesicular mechanism that shifts the voltage activation curve of calcium channels on cone axon terminals to more negative potentials (Verweij et al, 1996;Kraaij et al, 1999;Hirasawa and Kaneko, 2003;Cadetti and Thoreson, 2006). This shift opens calcium channels, causing a depolarization that opposes the light-induced photoreceptor hyperpolarization.…”