Abstract
Purpose: :
Light depolarizes retinal On bipolar cells by inactivating the mGluR6-mediated signaling cascade and opening a non-selective cation channel. We previously showed that a prolonged simulated-light stimulus results in a Ca2+-dependent depression of the postsynaptic response of On bipolar cells, perhaps due to desensitization of the transduction channel. A desensitization of the transduction current would result in repolarization of the On bipolar cell, and consequently a reduction in transmitter release onto postsynaptic ganglion cells. Here, we test the possibility that such a mechanism could contribute toward the transient properties of ganglion cell light responses.
Methods: :
Whole-cell voltage clamp recordings were made from ganglion cells in acute tiger salamander retinal slices. Slices were bathed in the mGluR6 agonist L-AP4 to keep the transduction channel in On bipolar cells closed, mimicking darkness. EPSCs were evoked by depolarization of presynaptic On bipolar cells with the mGluR antagonist LY341495. Responses were measured in the presence and absence of inhibitory feedback from amacrine cells, and AMPAR desensitization.
Results: :
Our results show that under continuous simulated-light conditions On bipolar cell desensitization contributes to the shaping of ganglion cell responses. The decay rate of EPSCs was 70±15ms under conditions where feedback from amacrine cells was intact. When feedback was removed using picrotoxin and strychnine, the EPSC amplitude increased by approximately 75% but the decay rate was not significantly affected (119±68ms; p>0.45 compared with control). In addition, AMPAR desensitization could not account for the decay of the EPSC observed in ganglion cells. This suggests that feedback occurs on a fast time scale, strongly attenuating the initial phase of the EPSC while On bipolar cell desensitization impacts the decay phase of the EPSC.
Conclusions: :
We find that desensitization plays a major role in On bipolar cell signaling to ganglion cells. Though inner retinal inhibition does modulate the responses but it occurs at a different time scale. Specifically, the effect of feedback inhibition on signaling occurs very rapidly whereas desensitization develops slowly and has a longer-lasting effect.
Keywords: bipolar cells • ganglion cells • receptors: pharmacology/physiology