The complexity of the internal structure of the striatum is not completely understood, and the striosomes/matrix compartmentalization in particular has been one of the intriguing substructures of the striatum. Although various neurochemical markers have been used to visualize striosomes with sufficient clarity, it still remains obscure whether striosomes that are detectable by a single marker represent all of the striosomal compartments and to what extent the compartments are uniform across different intrastriatal positions. Triple immunohistochemical labeling for the three representative striosomes/matrix markers, μ-opioid receptor (MOR), substance P (SP), and enkephalin (Enk), was applied to serial sections covering the whole striatum of the mouse (n=8). The majority of MOR-positive striosomes were confined to the rostral quarter of the striatum. In contrast, SP-positive striosomes were distributed more broadly in the rostral two-thirds of the striatum. No striosomes were observable in the caudal third by the present method. In the rostral striatum, the majority of striosomes were labeled for both MOR and SP, but some at the most rostral positions were detectable only by MOR, while caudally located striosomes were identifiable only by SP. Thus MOR- and SP-immunoreactivities in striosomes exhibited contrasting patterns along the rostrocaudal axis. The Enk immunohistochemistry produced complicated profiles and was unsuitable for the detection of striosomes in mice. However, Enk immunoreactivity in MOR and/or SP-positive striosomes was higher in the ventral portion than in the dorsal portion in the rostral striatum. The present study revealed the region-specific diversity of striosomes, suggesting site-dependent differential regulation of striosomal neurons by MOR ligands and SP that are contained in indirect- and direct-pathway neurons, respectively. The results further suggest the necessity of viewing the striosomes as non-uniform compartments in addition to the traditional dichotomous view, which focuses on discrimination between the striosomes and the matrix.
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