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      Expression of feeding-related neuromodulatory signalling molecules in the mouse central olfactory system

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          Abstract

          Various neural systems cooperate in feeding behaviour, and olfaction plays crucial roles in detecting and evaluating food objects. While odour-mediated feeding behaviour is highly adaptive and influenced by metabolic state, hedonic cues and learning processes, the underlying mechanism is not well understood. Feeding behaviour is regulated by orexigenic and anorexigenic neuromodulatory molecules. However, knowledge of their roles especially in higher olfactory areas is limited. Given the potentiation of feeding behaviour in hunger state, we systemically examined the expression of feeding-related neuromodulatory molecules in food-restricted mice through quantitative PCR, in the olfactory bulb (OB), olfactory tubercle (OT), and remaining olfactory cortical area (OC). The OT was further divided into attraction-related anteromedial, aversion-related lateral and remaining central regions. Examination of 23 molecules including neuropeptides, opioids, cannabinoids, and their receptors as well as signalling molecules showed that they had different expression patterns, with many showing elevated expression in the OT, especially in the anteromedial and central OT. Further, in mice trained with odour-food association, the expression was significantly altered and the increase or decrease of a given molecule varied among areas. These results suggest that different olfactory areas are regulated separately by feeding-related molecules, which contributes to the adaptive regulation of feeding behaviour.

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          Most cited references39

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          Dopamine reward circuitry: two projection systems from the ventral midbrain to the nucleus accumbens-olfactory tubercle complex.

          Anatomical and functional refinements of the meso-limbic dopamine system of the rat are discussed. Present experiments suggest that dopaminergic neurons localized in the posteromedial ventral tegmental area (VTA) and central linear nucleus raphe selectively project to the ventromedial striatum (medial olfactory tubercle and medial nucleus accumbens shell), whereas the anteromedial VTA has few if any projections to the ventral striatum, and the lateral VTA largely projects to the ventrolateral striatum (accumbens core, lateral shell and lateral tubercle). These findings complement the recent behavioral findings that cocaine and amphetamine are more rewarding when administered into the ventromedial striatum than into the ventrolateral striatum. Drugs such as nicotine and opiates are more rewarding when administered into the posterior VTA or the central linear nucleus than into the anterior VTA. A review of the literature suggests that (1) the midbrain has corresponding zones for the accumbens core and medial shell; (2) the striatal portion of the olfactory tubercle is a ventral extension of the nucleus accumbens shell; and (3) a model of two dopamine projection systems from the ventral midbrain to the ventral striatum is useful for understanding reward function. The medial projection system is important in the regulation of arousal characterized by affect and drive and plays a different role in goal-directed learning than the lateral projection system, as described in the variation-selection hypothesis of striatal functional organization.
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            D1 and D2 dopamine receptor-regulated gene expression of striatonigral and striatopallidal neurons

            The striatum, which is the major component of the basal ganglia in the brain, is regulated in part by dopaminergic input from the substantia nigra. Severe movement disorders result from the loss of striatal dopamine in patients with Parkinson's disease. Rats with lesions of the nigrostriatal dopamine pathway caused by 6-hydroxydopamine (6-OHDA) serve as a model for Parkinson's disease and show alterations in gene expression in the two major output systems of the striatum to the globus pallidus and substantia nigra. Striatopallidal neurons show a 6-OHDA-induced elevation in their specific expression of messenger RNAs (mRNAs) encoding the D2 dopamine receptor and enkephalin, which is reversed by subsequent continuous treatment with the D2 agonist quinpirole. Conversely, striatonigral neurons show a 6-OHDA-induced reduction in their specific expression of mRNAs encoding the D1 dopamine receptor and substance P, which is reversed by subsequent daily injections of the D1 agonist SKF-38393. This treatment also increases dynorphin mRNA in striatonigral neurons. Thus, the differential effects of dopamine on striatonigral and striatopallidal neurons are mediated by their specific expression of D1 and D2 dopamine receptor subtypes, respectively.
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              Stress, glucocorticoids and memory: implications for treating fear-related disorders

              Glucocorticoid stress hormones are crucially involved in modulating mnemonic processing of emotionally arousing experiences. They enhance the consolidation of new memories, including those that extinguish older memories, but impair the retrieval of information stored in long-term memory. As strong aversive memories lie at the core of several fear-related disorders, including post-traumatic stress disorder and phobias, the memory-modulating properties of glucocorticoids have recently become of considerable translational interest. Clinical trials have provided the first evidence that glucocorticoid-based pharmacotherapies aimed at attenuating aversive memories might be helpful in the treatment of fear-related disorders. Here, we review important advances in the understanding of how glucocorticoids mediate stress effects on memory processes, and discuss the translational potential of these new conceptual insights.
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                Author and article information

                Contributors
                yamaguchi@kochi-u.ac.jp
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                21 January 2020
                21 January 2020
                2020
                : 10
                : 890
                Affiliations
                [1 ]ISNI 0000 0001 0721 8377, GRID grid.452488.7, Institute of Food Sciences and Technologies, Ajinomoto Co., Inc., ; Kanagawa, Japan
                [2 ]Department of Physiology, Kochi Medical School, Kochi University, Kochi, Japan
                Article
                57605
                10.1038/s41598-020-57605-7
                6972952
                31964903
                63dd90e7-b0dd-496a-b1b2-225bbb9ce7d2
                © The Author(s) 2020

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 19 August 2019
                : 3 January 2020
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100001691, MEXT | Japan Society for the Promotion of Science (JSPS);
                Award ID: 16H01266
                Award ID: 19H03341
                Award Recipient :
                Categories
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                Custom metadata
                © The Author(s) 2020

                Uncategorized
                feeding behaviour,molecular neuroscience,neural circuits,olfactory cortex
                Uncategorized
                feeding behaviour, molecular neuroscience, neural circuits, olfactory cortex

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