The hippocampal formation and amygdala are responsible for regulating emotion, learning, and behavior. The hippocampal projection to the amygdala has been demonstrated to originate in the subiculum and adjacent portion of field CA1 of the Ammon's horn (Sub/CA1) in the rat; however, the topographical organization of this pathway is still understudied. To make it clear, we performed anterograde and retrograde tracing with biotinylated dextran amine (BDA) and cholera toxin B subunit (CTb), respectively, in the rat. A series of BDA experiments revealed that the temporal-to-septal axis of origin determined a medial-to-lateral axis of termination in the amygdala. Briefly, the temporal region of the Sub/CA1 projects preferentially to the medial amygdaloid region including the medial, intercalated, and basomedial nuclei and the amygdalohippocampal transition area, and progressively more septal portions of the Sub/CA1 distribute their efferents in more lateral regions of the amygdala. Sub/CA1 fibers distributed in the central amygdaloid nucleus were relatively few. Retrograde tracing with CTb confirmed this topography and revealed little hippocampal innervation of the central nucleus of the amygdala. These observations suggest that distinct Sub/CA1 regions arranged along the longitudinal hippocampal axis may influence distinct modalities of the amygdala function.

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The unexpected resistance of psoriasis lesions to fungal infections suggests local production of an antifungal factor. We purified Trichophyton rubrum-inhibiting activity from lesional psoriasis scale extracts and identified the Cys-reduced form of S100A7/psoriasin (redS100A7) as a principal antifungal factor. redS100A7 inhibits various filamentous fungi, including the mold Aspergillus fumigatus, but not Candida albicans. Antifungal activity was inhibited by Zn 2+, suggesting that redS100A7 interferes with fungal zinc homeostasis. Because S100A7-mutants lacking a single cysteine are no longer antifungals, we hypothesized that redS100A7 is acting as a Zn 2+ -chelator. Immunogold electron microscopy studies revealed that it penetrates fungal cells, implicating possible intracellular actions. In support with our hypothesis, the cell-penetrating Zn 2+ -chelator TPEN was found to function as a broad-spectrum antifungal. Ultrastructural analyses of redS100A7-treated T. rubrum revealed marked signs of apoptosis, suggesting that its mode of action is induction of programmed cell death. TUNEL, SYTOX-green analyses, and caspase-inhibition studies supported this for both T. rubrum and A. fumigatus. Whereas redS100A7 can be generated from oxidized S100A7 by action of thioredoxin or glutathione, elevated redS100A7 levels in fungal skin infection indicate induction of both S100A7 and its reducing agent in vivo. To investigate whether redS100A7 and TPEN are antifungals in vivo, we used a guinea pig tinea pedes model for fungal skin infections and a lethal mouse Aspergillus infection model for lung infection and found antifungal activity in both in vivo animal systems. Thus, selective fungal cellpenetrating Zn 2+ -chelators could be useful as an urgently needed novel antifungal therapeutic, which induces programmed cell death in numerous fungi.antifungal | innate immunity | epithelial defense | psoriasin | S100A7

It has been demonstrated that the spinal cord oligodendrocytes in the vertebrates arise in the ventral ventricular zone adjacent to the floor plate in their early development. Because of the similarities of basic structures in the spinal cord and metencephalon, it is probable that the mode of early oligodendrocyte development in the metencephalon is the same as that in the spinal cord. We examined this possibility in chick embryos, using monoclonal antibodies O1 and O4, markers for oligodendrocyte lineage. An O4-positive (O4+) cell focus was observed in the medial ventricular zone of E5 chick ventral metencephalon (the earliest stage examined), adjacent to the floor plate. At E6, O4+ cells were dispersed from the medial to the lateral pons and, at E7, to the cerebellar anlagen. O4+ cells in the E6 brainstem and in the E7 cerebellum were unipolar in shape, whereas one day later, some of the labeled cells were multipolar with a few thin processes. O1+ oligodendrocytes first appeared at E8 in the ventromedial part of the pons and were distributed throughout the pons at E10 and in the cerebellum at E12. Explants from three subdivisions of the metencephalon (medial and lateral pons, and cerebellum) from E5 to E8 chick embryos were separately cultured to confirm the potential for generation of oligodendrocyte lineage. O4+ cells appeared in the culture of the E5 medial pons (the earliest stage examined), in the E6 lateral pons, and in the E7 cerebellum. In addition, E7 was the youngest stage from which cerebellar explants were able to generate O1+ oligodendrocytes. Our results clearly demonstrated the in vivo morphology of oligodendrocyte precursors in the metencephalon and their developmental appearance in a ventral-to-dorsal manner. From the bipolar morphology of O4+ cells and the spacio-temporal continuity of the dispersion, it is inferred that the initial dispersion of O4+ cells may involve oligodendrocyte migration from the focus of the medial pons to the lateral and dorsal parts of the metencephalon.