The Journal of comparative neurology
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Members of the Eph family of receptor tyrosine kinases and their ligands, the ephrins, are expressed in distinct patterns in the forming cortex. EphA7 is expressed early in cortical development, becoming concentrated in anterior and posterior domains, whereas ephrin-A5 is expressed later in corticogenesis, highest in the middle region that has low levels of EphA7. The EphA7 gene produces full-length and truncated isoforms, which are repulsive and adhesive, respectively. ⋯ In contrast, EphA7 appears to mediate permissive interactions in the postnatal cortex: the area of somatosensory cortex was significantly reduced in EphA7-/- mice. A similar reduction was present in ephrin-A5-/- animals and a more pronounced decrease was observed in EphA7/ephrin-A5-/- cortex. Taken together, this study supports a role for EphA7 and ephrin-A5 in the establishment and maintenance of certain cortical domains and suggests that the nature of their interactions changes with cortical maturity.
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Previous studies have demonstrated that morphine, administered systemically or directly into the periaqueductal gray (PAG), produces a significantly greater degree of antinociception in males in comparison with females. Because the midbrain PAG and its descending projections to the rostral ventromedial medulla (RVM) constitute an essential neural circuit for opioid-based analgesia, the present studies were conducted to determine whether sex differences in the anatomical organization of the PAG-RVM pathway, and its activation during persistent inflammatory pain, could account for sex-based differences in opioid analgesia. In the rat, retrograde tracing was combined with Fos immunocytochemistry to investigate sexual dimorphism in the organization of the PAG-RVM circuit and its activation by persistent inflammatory pain induced by intraplantar injection of complete Freund's adjuvant (CFA). ⋯ While no sex differences were noted in the activation of the PAG by persistent inflammatory pain, significantly more PAG-RVM cells were activated in males in comparison with females. Systemic administration of morphine significantly suppressed CFA-induced Fos in the PAG in males only. The results of these studies demonstrate that both the anatomical organization and the functional activation of the PAG-RVM circuit are sexually dimorphic and may provide the anatomical substrate for sex-based differences in morphine analgesia.