The distribution of tyrosine hydroxylase-immunoreactive fibers in the human entorhinal cortex

The entorhinal cortex plays an important role in learning and memory, and it has been implicated as a site of dysfunction in some neuropsychiatric disorders such as schizophrenia. The organization of many components of the neural circuitry of this region, including dopaminergic afferents, has not been studied in detail. Using immunohistochemical techniques, we examined the density and laminar distribution of axons immunoreactive for tyrosine hydroxylase, the rate limiting enzyme in catecholamine biosynthesis, in the entorhinal cortex of eight control human brains. The density of tyrosine hydroxylase-containing axons decreased from rostral to caudal regions of entorhinal cortex. In addition, there was a prominent medial to lateral gradient of increasing fiber density. This gradient extended into the adjacent transentorhinal cortex, which contained the highest density of labeled axons of the regions studied. The laminar distribution of tyrosine hydroxylase-containing fibers also differed among the subdivisions of the entorhinal cortex. A bilaminar pattern of labeled axons in layers deep I-superficial II and in deep layer VI was present in the intermediate and caudal subdivisions of entorhinal cortex. In contrast, the olfactory and rostral subdivisions, as well as portions of the transentorhinal region, contained a trilaminar pattern, with a high density of tyrosine hydroxylase-immunoreactive axons in layers deep I-superficial II, deep III-IV and deep VI. In addition, radially-oriented bands of labeled fibers were observed extending between deep layer I and layer III, particularly in the rostral subdivision of the entorhinal cortex. In summary, tyrosine hydroxylase-containing afferents to the human entorhinal cortex are distributed in a characteristic regional and laminar pattern, and the lateral regions of the entorhinal cortex and the adjacent transentorhinal cortex are particularly densely innervated. These data contribute to the understanding of the normal circuitry of the human entorhinal cortex, and are of potential relevance to the pathophysiology of certain neuropsychiatric disorders, such as schizophrenia.