Circadian Clock Regulation of Cone to Cone Horizontal Cell Synaptic Transfer in the Goldfish Retina

Abstract

Purpose: : A circadian clock in the goldfish retina regulates rod-cone coupling by activating dopamine D₂-like receptors in the day, so that coupling is weak during the day and remarkably strong at night (Ribelayga et al., 2008). The increase in rod-cone coupling at night shapes the light responses of the second-order cell, the pure-cone connected cone horizontal cell (cHC), which is dominated by rod input at night but receives no rod input during the day (Wang and Mangel, 1996). Here we sought to examine whether the clock affects synaptic transfer from cones to cHCs.

Methods: : Experiments were performed on superfused, isolated neural goldfish retinas during the subjective day and subjective night. Whole-cell, patch-clamp and fine-tipped, intracellular recordings were obtained from cone inner segments and L-type (H1) cHCs, respectively. Responses to dim full-field white and spectral light stimuli were measured.

Results: : First, we found that the dark-adapted synaptic transfer function was non-linear during the day, with a high gain for low intensity stimuli and a low gain for high intensity stimuli, ranging from 2.5 to 1. In contrast, the dark-adapted transfer function was lower (~ 0.4) and constant at night, independent of light intensity. Second, although the light response latency of dark-adapted cHCs was similar to that of cones during the day, it was ~ 40 ms longer at every stimulus intensity compared to that of cones at night. The response latency of rod HCs was similar in the day and night. Finally, application of the dopamine D₂-like receptor antagonist spiperone during the day altered signal transfer from cones to cHCs to that observed at night.

Conclusions: : These findings indicate that the retinal circadian clock controls synaptic transfer from cones to cHCs by activating D₂-like receptors during the day but not at night. Because D₂-like receptors are expressed by photoreceptors and not by cHCs, the clock likely regulates cone to cHC synaptic activity primarily at the cone pedicle. Our results are consistent with the recent finding that the implicit time of the human photopic b-wave increases at night (Hankins et al., 2001).

Keywords: circadian rhythms • horizontal cells • retinal connections, networks, circuitry