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In previous studies, fibers demonstrating somatostatin-like immunoreactivity were observed in the outer half of the molecular layer of the dentate gyrus in the rat and monkey. They occupy the same region as those of the perforant pathway that originates in the entorhinal cortex. Numerous somatostatin immunoreactive neuronal cell bodies were also observed in the hilar region, though stained axonal profiles could not be followed from these cells into the molecular layer. In the present study, several experimental procedures were employed to determine the origin of the somatostatin-positive fibers in the molecular layer. Transection of the perforant path fibers resulted in such characteristic changes as shrinkage of the molecular layer and sprouting of AChE-positive fibers. There was no apparent decrease, however, in the density of somatostatin-positive fibers. In fact, since the stained fibers occupied a narrower band in the shrunken molecular layer, their density appeared greater. Injections of kainic acid into the hilar region produced a lesion of hilar neurons, including those positive for somatostatin. In the region of cell loss, there was a marked reduction of somatostatin-immunoreactive fibers in the ipsilateral molecular layer, with no detectable changes in the homotopic contralateral molecular layer. The distribution of AChE fibers, which presumably have an extrinsic origin, was not altered by the treatment. In a final series of experiments, the retrograde tracer wheat germ agglutinin-horseradish peroxidase (WGA-HRP) was injected into the hilar region and sections were prepared for the simultaneous demonstration of the tracer and of somatostatin-like immunoreactivity. Somatostatin-positive neurons demonstrating WGA-HRP reaction product were observed primarily in the ipsilateral hilar region, but a few double-labeled cells were also seen in the same area of the contralateral side. These studies indicate that a population of intrinsic neurons located in the polymorphic layer of the dentate gyrus projects to the outer half of the ipsilateral molecular layer. A similar, but very much smaller, projection also extends to the contralateral dentate gyrus. Taken together, these projections appear to account for much of the somatostatin-like immunoreactivity in the molecular layer of the dentate gyrus.

An experimental analysis of the origins of somatostatin-like immunoreactivity in the dentate gyrus of the rat