Immunohistochemical localization of serotonin nerve terminals in the lateral entorhinal cortex of the rat: demonstration of two separate patterns of innervation from the midbrain raphe.

The distribution of serotonin (5-hydroxytryptamine, 5HT) containing nerve terminals in the lateral entorhinal cortex (LEC) has been studied using antibodies against 5-HT in combination with fluorescence histochemistry. Thin, varicose, branching fibers were found to be distributed in a relatively even, diffuse pattern throughout all layers of the LEC. The largest amount of this type of 5HT innervation was in Layer I. This diffuse pattern of 5-HT terminals was supplemented by a dense network of 5HT terminals restricted to Layer III of a small (approximately 1 mm) strip of the LEC. The fibers in this layer were thicker and more convoluted and contained larger varicosities than fibers in any other layer. The existence of a distinct innervation by 5-HT terminals of only a small portion of the LEC demonstrates a hitherto unrecognized and important principle of heterogeneity in 5-HT innervation of cortex. It suggests that 5-5HT neurons in the raphe can selectively influence specific, narrow regions of the lateral perforant path system, which, in turn, affect the intrinsic hippocampal circuits.