By the late 1990's, it was thus evident that the arcuate nucleus plays a central role in the initiation of the body's response to starvation. Still, it was not known which brain regions lie downstream in the circuitry. Only the dorsomedial and paraventricular hypothalamic nucleus had been anatomically identified as direct targets of the arcuate nucleus NPY neurons.114 Injection of NPY into these structures had also been reported to elicit feeding responses. However, the most potent stimulation of food intake behaviour was seen with highly localized injections into the perifornical area.107 In addition, one often overlooked aspect of the hypothalamic lesion studies is the observation that the hyperphagic phenotype observed following ablations involving the arcuate nucleus disappears with subsequent destruction of the LHA,4,5 indicating a hierarchical organization with the LHA operating downstream of the ventromedial complex. These results, in combination with the identification of two orexigenic peptides in separate LHA populations, suggested the existence of a direct arcuate-lateral hypothalamic pathway.
Histochemical evidence for such a projection was presented concurrently in two independent studies which demonstrated that NPY- as well as a-MSH-ir terminals cluster in dense plexuses in the rat LHA where they form close appositions onto both Hcrt and MCH neurons,31,33 see also refs 100, 91 (Fig. 3 a-d).
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