Hypothalamic dorsomedial nucleus neurons innervate thyrotropin-releasing hormone-synthesizing neurons in the paraventricular nucleus

To determine whether the hypothalamic dorsomedial nucleus (DMN) may serve a s a relay center for the central actions of leptin on thyrotropin-releasing hormone (TRH)-synthesizing neurons in the paraventricular nucleus (PVN), a xonal projections from the DMN to TRH-containing neurons in the PVN were st udied using the anterogradely transported marker substance, Phaseolus vulga ris-leucoag-glutinin (PHA-L). Stereotaxic injections of PKA-L were targeted to the mid-dorsal and mid-ventral portions of the DMN. After 10-14-day sur vival, the brains were prepared for immunohistochemistry and immunostained with an antibody directed against PHA-L. Focal injections confined to the D MN were identified in 14 animals and gave rise to a fiber bundle that enter ed the PVN at the caudal pole of the nucleus, densely innervating all parvo cellular subdivisions of the PVN. In double-labeled preparations using anti sera to PHA-L and preproTRH 178-199, the latter as a marker for TRH-contain ing neurons in the PVN, proTRH-IR neurons were observed to be enmeshed in a network of PHA-L-containing fibers. When the injection site covered the en tire DMN or the mid-dorsal part of the DMN, PHA-L-containing axon Varicosit ies were juxtaposed to similar to 97 and 90% of proTRH neurons, respectivel y, in all parvocellular subdivisions of the PVN, and by ultrastructural ana lysis were shown to be synaptic. In contrast, when the injection site was c entered primarily in the mid-ventral part of the DMN, only similar to 52% o f proTRH-synthesizing neurons appeared to be innervated by PHA-L-containing axons. These data demonstrate that a major projection pathway exists from the DMN, specifically to TRH-producing neurons in the PVN, and suggest that the DMN is anatomically situated to exert a regulatory effect on TRH-synth esizing neurons in the PVN. (C) 2001 Elsevier Science BN. All rights reserv ed.