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Ghrelin-containing neurons in the olfactory bulb send collateralized projections into medial amygdaloid and arcuate hypothalamic nuclei: neuroanatomical study

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Abstract

Ghrelin, a gastrointestinal hormone, is a modulator of the sense of smell. The main source of ghrelin in the central nervous system has been mainly observed in specific populations of hypothalamic neurons. An increasing number of studies have reported ghrelin synthesis and its effect on neurons outside the hypothalamus. Ghrelin and its receptors are expressed in the olfactory bulbs and in other centres of the brain, such as the amygdala, for processing olfactory signals, pyramidal neurons of the cerebral cortex and the dorsal vagal complex of the medulla oblongata. It is known that ghrelin is involved in cognitive mechanisms and eating behaviours, in fact, its expression increases in anticipation of food intake. In order to identify the existence of centrifugal direct afferents from the main olfactory bulb to the medial amygdala and the hypothalamus arcuate nucleus, in this work we used two retrograde tracers, Dil and Fluoro Gold, and immunohistochemical procedure to visualize positive ghrelin neurons. Our paper provides neuroanatomic support for the ghrelin modulation of smell. Our results show that ghrelin neuron projections from mitral cells of bulbs can transmit olfactory information via branching connections to the amygdala and the hypothalamus. This pathway could play an important role in regulating feeding behaviour in response to odours.

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Fig. 1

(modified from Paxinos and Watson 1998); C, D Representative injection sites: fluorescent micrograph of examples of Dil injected area (Me); fluorescent micrograph of examples of FG injected area (ARH). Scale bar, 200 µm. E Coronal diagram of ipsilateral projection from the olfactory bulb to the Me and ARH. Symbols indicate the location of labelled cells in the mitral cell layer (MCL): blue dot = single-FG-labelled neurons (FG-slMC); red dot = single-Dil-labelled neurons (Dil-slMC); blue and red concentric circle = double-FG/Dil-labelling neurons (dlMC); blue, red and green concentric circle = FG/Dil/FITC triple-labelled neurons (tlMC). Each symbol is equivalent to one labelled neuron. F: Fluorescent micrograph (magnification ×4) indicates the (a) Dil and (b) FG labelled layer (MCL) of the MOB: arrows = dlMC; rhomb = Dil-slMC; asterisk = FG-slMC. G: Example of FG/Dil/FITC triple-labelled neuron in the MOB (size 25 µm). H Example of single-Dil-labelled neurons in the MOB (size 20 µm). I Example of single-FG-labelled neurons in the MOB (size 20 µm). L Example of double-FG/Dil-labelling neurons in the MOB (size 10 µm). Scale bar 10 µm

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Acknowledgements

This research was supported by Ministero Istruzione, Università e Ricerca (MIUR). We wish to thank the Scientific Bureau of the University of Catania for language support.

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Correspondence to Stefania Stanzani.

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Russo, C., Russo, A., Pellitteri, R. et al. Ghrelin-containing neurons in the olfactory bulb send collateralized projections into medial amygdaloid and arcuate hypothalamic nuclei: neuroanatomical study. Exp Brain Res 236, 2223–2229 (2018). https://doi.org/10.1007/s00221-018-5298-z

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