Biology subjects

Solessio, E.

Publications and source records attributed to Solessio, E..

3 recordsLinked to original sources

bioRxiv2025

Retinal Cx36 gap junctions in the inner and outer plexiform layers differentially control visual thresholds.

Gap junctions are an important component of signal communication in sensory systems. In the retina, connexin 36 (Cx36) gap junctions integrate visual signals over space and time. However, we do not understand how Cx36 gap junctions in the inner- and outer-retina govern visual thresholds under dim light conditions. Here we address this question using transgenic mouse models, a state-of-the-art operant behavioral assay, and psychophysical modelling. Visual thresholds with Ganzfeld illumination decreased steeply (- 2 log/dec) with flash durations < 0.5 s, reaching an asymptotic value of[~] 2 x 10-4photons/{micro}m2/s with longer flashes. Temporal summation and photon noise modelled under Signal Detection Theory account for the observed thresholds. Removal of outer-retinal Cx36 lowers visual thresholds by 2.6-fold. Nested model analysis suggests that the probability of transmission of single photon signals between rods and bipolar cells increases in the absence of CX36 gap junctions between rods and cones. Removal of Cx36 in both the inner and outer retina increases visual thresholds by 16.5-fold, consistent with a loss of spatial-averaging and reduction of neural noise by Cx36 in the inner-retina. We conclude that both inner- and outer-retinal Cx36 control visual thresholds under dim light conditions, but in distinct ways. Outer-retinal Cx36 increases thresholds, perhaps in a necessary tradeoff that provides rod signals access to the alternative rod-cone pathway, whereas inner-retinal Cx36 decreases thresholds by increasing spatial-integration, more than compensating for outer retina losses.

neuroscience↗

bioRxiv2021

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

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

neuroscience↗

bioRxiv2021

Differential impact of Kv8.2 loss on rod and cone signaling and degeneration.

Heteromeric Kv2.1/Kv8.2 channels are voltage-gated potassium channels localized to the photoreceptor inner segment. They carry IKx, which is largely responsible for setting the photoreceptor resting membrane potential. Mutations in Kv8.2 result in childhood-onset Cone Dystrophy with Supernormal Rod Response (CDSRR). We generated a Kv8.2 knockout (KO) mouse and examined retinal signaling and photoreceptor degeneration to gain deeper insight into the complex phenotypes of this disease. Using electroretinograms we show that there were delayed or reduced signaling from rods depending on the intensity of the light stimulus, consistent with reduced capacity for light-evoked changes in membrane potential. The delayed response was not seen ex vivo where extracellular potassium levels were controlled by the perfusion buffer, so we propose the in vivo alteration is influenced by genotype-associated ionic imbalance. We observed mild retinal degeneration. Signaling from cones was reduced but there was no loss of cone density. Loss of Kv8.2 altered responses to flickering light with responses attenuated at high frequencies and altered in shape at low frequencies. The Kv8.2 KO line on an all-cone retina background had reduced cone-driven ERG b wave amplitudes and underwent degeneration. Altogether, we provide insight into how a deficit in the dark current affects the health and function of photoreceptors.

neuroscience↗