Temporal Contrast Enhancement via GABA_C Feedback at Bipolar Terminals in the Tiger Salamander Retina

Abstract

Most retinal amacrine (ACs) and ganglion cells (GCs) express temporal contrast by generating action potentials at only the onset and offset of the light stimulus. This study investigated the neural mechanisms that underlie this temporal contrast enhancement. Whole cell patch recordings were made from bipolar cells (BCs), ACs, and GCs in the retinal slice preparation. The cells were identified by the locations of their somas in the inner nuclear layer and ganglion cell layers, their characteristic light responses, and morphology revealed by Lucifer yellow staining. Depolarizing a single BC with a brief voltage pulse elicited a Cl- tail current that was completely abolished when Ca2+ entry to bipolar terminals was prevented, by either removing Ca2+ from the Ringer solution or blocking Ca2+ channels with Co2+. This suggests that the Cl- current is Ca2+-dependent. In those bipolar cells whose axon terminals were cutoff during slicing no Cl- current was observed, indicating that this current is generated at the synaptic terminals. The Cl- current consists of a predominant synaptic component that can be blocked by the non-N-methyl--aspartate (NMDA) glutamate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) or by the gamma-aminobutyric acid-C (GABAC) receptor antagonist picrotoxin. There also exists a relatively small nonsynaptic component. Thus both glutamatergic and GABAergic transmission were involved in the generation of this Cl- current, suggesting that it is mediated by a recurrent feedback to bipolar cells. Picrotoxin, which blocks both GABAC receptors at BC terminals and GABAA receptors on the dendrites of ACs and GCs, converted the light-elicited voltage response in most - ACs and GCs from transient to sustained. Bicuculline, which blocks only the GABAA receptors, did not prolong the transient response in - ACs and GCs. This suggests that a negative feedback mediated by the GABAC receptor on the bipolar terminals is responsible for making these responses transient. After the GABAergic feedback was blocked with picrotoxin the light-elicited voltage responses (recorded under current clamp) were more sustained than the current responses (recorded under voltage clamp) to the same light stimuli. This suggests that a voltage-dependent conductance converts the relatively transient current responses to more sustained voltage responses. Our results imply a synaptically driven local GABAergic feedback at bipolar terminals, mediated by GABAC receptors. This feedback appears to be a significant component of the mechanism underlying temporal contrast enhancement in - ACs and GCs.

GABACReceptors Control Adaptive Changes in a Glycinergic Inhibitory Pathway in Salamander Retina

“…Similar changes in the amplitude and kinetics of glycinergic responses by GABA antagonists in light-adapted preparations were attributed to blocking GABA A receptors on glycinergic amacrine cells (Zhang et al, 1997;Roska et al, 1998). Blocking GABA C receptors on bipolar terminals, which increases excitatory input from bipolar cells to third-order neurons Dong and Werblin, 1998), could also cause a rapid increase in glycinergic IPSCs. The fact that picrotoxin never caused a rapid enhancement of glycinergic IPSCs in dark-adapted retinas supports the idea that in dark-adapted retinas the glycinergic amacrine cells are suppressed by a separate action of GABA.…”

“…The immediate block of ganglion cell responses to GABA puffs indicates that GABA A receptors were rapidly blocked. Because GABAergic feedback to bipolar cell terminals in salamander retina is mediated mainly by GABA C receptors (L ukasiewicz et al, 1994;Dong and Werblin, 1998) the rapid enhancement of EPSC s indicates that GABA C receptors were also rapidly blocked. Other studies have also shown that GABA C receptors are rapidly blocked by picrotoxin (C. R. Shields and P. D. Lukasiewicz, unpublished observations) (see also Feigenspan and Bormann, 1994).…”

c-Fos expression in the visual system of the tree shrew (Tupaia belangeri)

“…In contrast, lateral inhibition in the IPL, which contributes to the surround of ganglion cells, is mediated by GABA (Cook and McReynolds, 1998;Flores-Herr et al, 2001). In addition, GABAergic inhibition in the IPL also may shape the temporal responses of ganglion cells (Dong and Werblin, 1998) and is a key player in the signaling that determines their motion and direction sensitivity (Caldwell et al, 1978).…”

Spike-Dependent GABA Inputs to Bipolar Cell Axon Terminals Contribute to Lateral Inhibition of Retinal Ganglion Cells

“…The GABA receptors, which mediate these two types of inhibition, are different. IPSCs in ganglion cells are mediated by GABA A receptors, whereas IPSCs in bipolar cells are mediated mainly by GABA C receptors (Dong and Werblin 1998;Ichinose and Lukasiewicz 2002;Lukasiewicz and Shields 1998). In addition, the amacrine cell types that contact bipolar and ganglion cells may be different.…”