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bioRxiv · 10.1101/2021.11.03.467151

Cone-driven retinal responses are shaped by rod but not cone HCN1

Lankford, C.·Umino, Y.·Poria, D.·Kefalov, V.·Solessio, E.·Baker, S. A.
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Abstract

Signal integration of converging neural circuits is poorly understood. One example is in the retina where the integration of rod and cone signaling is responsible for the large dynamic range of vision. The relative contribution of rods versus cones is dictated by a complex function involving background light intensity and stimulus temporal frequency. One understudied mechanism involved in coordinating rod and cone signaling onto the shared retinal circuit is the hyperpolarization activated current (Ih) mediated by HCN1 channels. Ih opposes membrane hyperpolarization driven by activation of the phototransduction cascade and modulates the strength and kinetics of the photoreceptor voltage response. We examined conditional knockout of HCN1 from rods using electroretinography. In the absence of HCN1, rod responses are prolonged in dim light which altered the response to slow modulation of light intensity both at the level of retinal signaling and behavior. Under brighter intensities, cone-driven signaling was suppressed. To our surprise, conditional knockout of HCN1 from cones had no effect on cone-mediated signaling. We propose that Ih is dispensable in cones due to the high level of temporal control of cone phototransduction. Thus, HCN1 is required for cone-driven retinal signaling only indirectly by modulating the voltage response of rods to limit their output. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=101 SRC="FIGDIR/small/467151v1_ufig1.gif" ALT="Figure 1"> View larger version (21K): org.highwire.dtl.DTLVardef@1aa760borg.highwire.dtl.DTLVardef@2be292org.highwire.dtl.DTLVardef@1280235org.highwire.dtl.DTLVardef@1a8f487_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Lankford, C., Umino, Y., Poria, D., Kefalov, V., Solessio, E., Baker, S. A.. 2021-11-04. Cone-driven retinal responses are shaped by rod but not cone HCN1. https://doi.org/10.1101/2021.11.03.467151

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