Synaptic transmission of visual signals begins at the photoreceptor-bipolar cell synapse in the retina. A key presynaptic structure of photoreceptors and bipolar cells is the synaptic ribbon (SR), the function of which remains largely speculative. We set out to explore the function of the SR by studying the hibernating ground squirrel (GS) retina, in which the SRs undergo drastic structural changes. In hibernating GSs, confocal images show that a large amount of SRs disengage from the cytomatrix active zone (CAZ) and aggregate into a """"""""large sphere"""""""" that resides several microns above the base of the cone terminal. EM images indicate that the """"""""large sphere"""""""" is composed of many small ribbon fragments. Surprisingly though, when depolarizing voltage steps are applied to cones, large excitatory postsynaptic potentials (EPSCs) can still be elicited from the postsynaptic bipolar cells;even though immune-staining performed after the recording indicates that the labeling of the SR is greatly reduced. Quantal miniature EPSCs in hibernating GSs are comparable in size and kinetics with those in awake GSs, but are reduced in frequency. The size of the readily releasable pool (RRP) of vesicles at the hibernating cone ribbon synapse decreases significantly. The rate of vesicle replenishment, which is reflected by the recovery rate of the paired-pulse depression, is slower in the hibernating GSs compared with that in the awake GSs. Accordingly, in GSs that were just awaken from hibernation, photopic full-field flash electroretinaogram (ERG) shows a normal waveform with a reduced amplitude and flicker ERG shows a significantly decreased critical fusion frequency. Biochemical studies indicate that the detachment of the ribbons from the CAZs during hibernation possibly involves dissociation of two proteins, ribeye and bassoon, which is regulated by NAD(H) binding and their ratio. These results indicate that, 1) photoreceptor ribbon synapses maintain their basic synaptic functions despite seasonal structural alterations that significantly reduce the size of the ribbons at the synapse;2) One function of SR is to facilitate the turnover of synaptic vesicles to ensure high frequency synaptic signaling;3) Ribeye, in addition to its role as a main structural component of the ribbon, may also act as a redox sensor, autonomously regulating its structure and distribution.
