In vivo studies of signaling in rod pathways of the mouse using the electroretinogram

Purpose: (a) To examine the possibility that there is a threshold in the synaptic mechanism linking rods to rod bipolar cells that can reduce the transmission of continuous noise from the rods without blocking the transmission of any significant proportion of single-photon responses. (b) To estimate the level of this threshold and the amplitude of the continuous noise which it can serve to reduce. (c) To identify the location of the threshold mechanism in the rod to rod bipolar cell pathway. Methods: Corneal electroretinogram recordings were made from dark-adapted mice anesthetized with ketamine/xylazine after inner-retinal components had been suppressed to isolate PII, the response of depolarizing bipolar cells. Suppression was achieved by intravitreal injections of GABA, TTX, or in Cx36 KO animals by crushing the optic nerve and waiting for ganglion cells to degenerate. Results: All energy-scaled records of isolated PII obtained with ganzfeld stimuli that gave rise to much less than one photoisomerization (R*) per rod (0.01-0.2 R*/rod), had an essentially identical waveform. Stronger stimuli caused a reduction in the peak amplitude of energy-scaled records (saturation) and stimuli strong enough to produce multiple isomerizations in individual rods resulted in a shortening of the response latency and an increase of the energy-scaled amplitude at early times (supralinearity). The shape of the rising edge of isolated PII changed with flash energy in a way that was consistent with the existence of a synaptic threshold whose level was less than one tenth of the amplitude of single-photon signals and a continuous noise whose rms amplitude was even less than this. However, when measured at the time of the peak, the amplitude of PII increased linearly in proportion to stimulus energy from the very lowest levels up to the point where there was, on average, 0.2 R*/rod. Conclusions: There is a threshold nonlinearity operating at the output of the rod to rod bipolar cell synapse that can usefully reduce the transmission of continuous rod noise without significantly affecting the transmission of single-photon signals. This nonlinearity does not affect the overall linear function of the rod pathway at levels at which it is effectively operating in a photon-counting mode. (C) 2004 Elsevier Ltd. All rights reserved.