Using immunolabeling, live cell calcium imaging, and whole cell patch clamp methods, we found that in RS1KO mice, rod-rod bipolar cell (RBC) synapses develop normally. However, synaptic abnormalities were detected at P22 before any overall structural change of the retina occurred. Specifically, we found that the presynaptic basal calcium concentration in rod terminals is significantly lower in KO mice. On the postsynaptic side, a key alteration is that TRPM1 channels, which are normally expressed at the dendritic tips of RBCs, are redistributed toward the dendritic shafts and soma of RBCs. Consistent with the presence of fewer channels, RBCs were found to be more hyperpolarized in the KO mice. These synaptic defects point to a weakened rod-RBC synapse, which may well be the underlying mechanism for the reduced b-wave amplitude in ERG measurements in the KO animals as well as in patients. Concurrently, a characteristic pattern of changes in molecules that are involved in the cascade between the glutamate receptors (mGluR6) and the channels (TRPM1) has been identified. These pre- and post-synaptic defects progress as the animal ages, tracking the functional defects measured by ERG. Most intriguingly, after resupplying the KO mice with RS1 genes delivered by AAV8-RS1 gene transfer, all of the synaptic defects were found to be significantly alleviated. Concomitantly, ERG b-wave amplitude and a-wave implicit time were substantially improved in a virus dose dependent fashion. These results are exciting, because they point to considerable plasticity in degenerative synapses that we can potentially harness for gene therapy or other interventions even at later stages of neurodegenerative diseases.