Altered morphology of rod bipolar cell axonal terminals in the retinas of mice carrying genetic deletion of somatostatin subtype receptor 1 or 2

Somatostatin (SRIF), similar to other neuropeptides, is likely to influence the morpho-functional characteristics of neurons. We studied possible morphological alterations of mouse retinal neurons following genetic deletion of SRIF subtype receptor 1 [sst(1) knockout (KO)] or 2 (sst(2) KO). In sst, KO retinas, axonal terminals of rod bipolar cells (RBCs), identified with protein kinase C immunoreactivity, were 25% larger than in controls. In contrast, in sst(2) KO retinas, RBC axonal terminals were significantly smaller <LF>(-14%). No major ultrastructural differences were observed between control and KO RBCs. In sst(2) KO retinas, SRIIF levels decreased by about 35%, while both sst(1) receptor mRNA and protein increased by about 170% and 100%, respectively This compares to previous results reporting an increase of both retinal SRIF and sst(2) receptors following sst(1) receptor deletion. Together, these findings suggest that, on the one hand, sst(1) receptor deletion induces over-expression of sst(2) receptors, and vice versa; on the other hand, that an imbalance in sst(1) and sst(2) receptor expression and/or changes in the levels of retinal SRIF induced by sst(1) or sst(2) receptor deletion are responsible for the morphological changes in RBC axonal terminals. Similar alterations of RBC terminals were observed in KO retinas at 2 weeks of age (eye opening). In addition, reverse transcription-polymerase chain reaction analysis of the expression of sst(2) and sst(1) receptors in developing sst(1) and sst(2) KO retinas, respectively, demonstrated that these receptors are up-regulated at or near eye opening. These findings suggest that the integrity of the somatostatinergic system during development is necessary for proper RBC maturation.