Adaptive changes of the ground squirrel retina during hibernation

National Eye Institute

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Abstract

We previously described structural changes in photoreceptor ribbons of the hibernating retina. We investigated the functional consequences of such structural alteration and identified a significant role of the ribbon in facilitating replenishment of the readily releasable pool of synaptic vesicles, thereby ensuring high frequency synaptic transmission. This finding at the synaptic level corresponds with those at the systemic level, considering that electroretinogram (ERG) recordings have revealed a significant decrease in the ability of hibernating eyes to detect high-frequency flicker. We also explored the potential molecular mechanism of this ribbon plasticity and discovered that the ratio of NADH+/NAD in the photoreceptor, which reflects its cellular metabolic state, regulates the interaction of ribeye, the main ribbon protein, with bassoon, another cytoplasmic active zone (CAZ) protein. Reduced interaction between ribeye and bassoon likely contributes to the destabilization of the ribbon structure. One reasonable argument is that, owing to the diminished ribbon structure in the hibernating condition, the synaptic activities we observed previously might originate from glutamate release at the site of membrane opposition between the cone photoreceptor and OFF bipolar cell dendrites, and therefore are not associated with synaptic ribbons. In the past year, we have conducted two sets of experiments to confirm that synaptic activities in the cone photoreceptors of hibernating retinas are indeed associated with synaptic ribbons. In the first set of experiments, we examined the kinetics of miniature-like responses from different types of OFF cone bipolar cells, which have been previously shown to have different amplitudes and kinetics due to their distinct distances from the site of glutamate release. If glutamate were released from the basal membrane instead of the site of ribbon, one would expect to see significant changes in kinetics and amplitudes of the miniature-like responses recorded from OFF cone bipolar cells that make contacts at the basal membrane. Nonetheless, the results show that, in hibernating tissues, OFF cone bipolar cells maintained their stereotypic kinetics and amplitude features as in the normal conditions. This indicates that the release likely occurs at the site of the ribbon. In a second set of experiments, we applied a fluorophore-assisted light inactivation (FALI) method to acutely damage the residual ribbon structure in the hibernating tissues. In so doing, the synaptic activities observed prior to light-inactivation of the ribbon were eliminated following FALI. Based on these results, we concluded that the plasticity of cone photoreceptor synaptic ribbons during hibernation provides a valid model to study the functions of the synaptic ribbon. We propose to build a computational model of the synaptic ribbon based on our structural data and existing parameters in the literature so that we can further investigate its function in transforming visual information.