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Abstract: Synaptic relationships between ghrelin-like immunoreactive axon terminals and other neurons in the hypothalamic arcuate nucleus (ARC) were studied using immunostaining methods at the light and electron microscope levels. Many ghrelin-like immunoreactive axon terminals were found to be in apposition to ghrelin-like immunoreactive neurons at the light microscopic level. At the electron microscopic level, ghrelin-like immunoreactive axon terminals were found to make synapses on ghrelin-like immunoreactive cell bodies and dendrites in the ARC. While the axo-dendritic synapses between ghrelin- and ghrelin-like immunoreactive neurons were mostly the asymmetric type, the axo-somatic synapses were both asymmetric and symmetric type of synapses. Ghrelin at 10−10 M increased cytosolic Ca2+ concentration ([Ca2+]i) in the neurons isolated from the ARC, some of which were immunocytochemically identified as ghrelin-positive. Ghrelin at 10−10 M also increased [Ca2+]i in 12% of ghrelin-like immunoreactive neurons in the ARC. These findings suggest that ghrelin serves as a transmitter and/or modulator that stimulates [Ca2+]i signaling in ghrelin neurons of the ARC, which may participate in the orexigenic action of ghrelin. Our data suggests a possibility of existing a novel circuit implicating regulation of feeding and/or energy metabolism. [Copyright &y& Elsevier]