Abstract
Following fasting, satiety is accompanied by neuronal activation in brain areas including the central amygdalar nucleus (CEA). Since CEA is known to inhibit food intake, we hypothesized that CEA contributes to the termination of meal during refeeding. To better understand the organization of this satiety-related circuit, the interconnections of the CEA with refeeding-activated neuronal groups were elucidated using retrograde (cholera toxin-β subunit, CTB) and anterograde (phaseolus vulgaris leucoagglutinin, PHA-L) tracers in male rats. C-Fos-immunoreactivity was used as marker of neuronal activation. The refeeding-activated input of the CEA primarily originated from the paraventricular thalamic, parasubthalamic and parabrachial nuclei. Few CTB-c-Fos double-labeled neurons were detected in the prefrontal cortex, lateral hypothalamic area, nucleus of the solitary tract (NTS) and the bed nuclei of the stria terminalis (BNST). Only few refeeding-activated proopiomelanocortin-producing neurons of the arcuate nucleus projected to the CEA. Anterograde tract tracing revealed a high density of PHAL-labeled axons contacted with refeeding-activated neurons in the BNST, lateral hypothalamic area, parasubthalamic, paraventricular thalamic and parabrachial nuclei and NTS; a low density of labeled axons was found in the paraventricular hypothalamic nucleus. Chemogenetic activation of the medial CEA (CEAm) inhibited food intake during the first hour of refeeding, while activation of lateral CEA had no effect. These data demonstrate the existence of reciprocal connections between the CEA and distinct refeeding-activated hypothalamic, thalamic and brainstem nuclei, suggesting the importance of short feedback loops in the regulation of satiety and importance of the CEAm in the regulation of food intake during refeeding.
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Acknowledgements
The authors are grateful for Vera Maruzs and Ágnes Simon for the expert technical assistant. This work was supported by Grants from the Hungarian Science Foundation (OTKA K109710), Hungarian National Brain Research Program, Lendület Award of the Hungarian Academy of Sciences, the Dr. Gerald J. and Dorothy R. Friedman New York Foundation for Medical Research and the NIDDK HD087958 Grant.
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GZ: anterograde tract tracing, comparing c-Fos immunoreactivity in fasted and refed animals in order to choose the areas of interest, DREADD virus injection, c-Fos analysis of DREADD virus-injected animals, immunohistochemistry, image preparation and analysis. BV: Retrograde tract tracing, DREADD virus injection, immunohistochemistry, image analysis. AS-S: analyses of feeding behavior. MT: analyses of feeding behavior. RML: data interpretation, manuscript preparation. CF: experimental design, data acquisition, drafting, revising and interpretation of the work, takes primary responsibility.
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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were reviewed and approved by the Animal Welfare Committee of the Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary.
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Zséli, G., Vida, B., Szilvásy-Szabó, A. et al. Neuronal connections of the central amygdalar nucleus with refeeding-activated brain areas in rats. Brain Struct Funct 223, 391–414 (2018). https://doi.org/10.1007/s00429-017-1501-4
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DOI: https://doi.org/10.1007/s00429-017-1501-4