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      Bidirectional control of fear memories by cerebellar neurons projecting to the ventrolateral periaqueductal grey

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          Abstract

          Fear conditioning is a form of associative learning that is known to involve different brain areas, notably the amygdala, the prefrontal cortex and the periaqueductal grey (PAG). Here, we describe the functional role of pathways that link the cerebellum with the fear network. We found that the cerebellar fastigial nucleus (FN) sends glutamatergic projections to vlPAG that synapse onto glutamatergic and GABAergic vlPAG neurons. Chemogenetic and optogenetic manipulations revealed that the FN-vlPAG pathway controls bi-directionally the strength of the fear memories, indicating an important role in the association of the conditioned and unconditioned stimuli, a function consistent with vlPAG encoding of fear prediction error. Moreover, FN-vlPAG projections also modulate extinction learning. We also found a FN-parafascicular thalamus pathway, which may relay cerebellar influence to the amygdala and modulates anxiety behaviors. Overall, our results reveal multiple contributions of the cerebellum to the emotional system.

          Abstract

          The cerebellum has a role in motor control, but may also contribute to other functions. Here the authors demonstrate a role for the cerebellar fastigial nucleus projection onto ventrolateral periaqueductal grey neurons during fear acquisition.

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            Memory--a century of consolidation.

            J McGaugh (2000)
            The memory consolidation hypothesis proposed 100 years ago by Müller and Pilzecker continues to guide memory research. The hypothesis that new memories consolidate slowly over time has stimulated studies revealing the hormonal and neural influences regulating memory consolidation, as well as molecular and cellular mechanisms. This review examines the progress made over the century in understanding the time-dependent processes that create our lasting memories.
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              Subcortical and cortical brain activity during the feeling of self-generated emotions.

              In a series of [15O]PET experiments aimed at investigating the neural basis of emotion and feeling, 41 normal subjects recalled and re-experienced personal life episodes marked by sadness, happiness, anger or fear. We tested the hypothesis that the process of feeling emotions requires the participation of brain regions, such as the somatosensory cortices and the upper brainstem nuclei, that are involved in the mapping and/or regulation of internal organism states. Such areas were indeed engaged, underscoring the close relationship between emotion and homeostasis. The findings also lend support to the idea that the subjective process of feeling emotions is partly grounded in dynamic neural maps, which represent several aspects of the organism's continuously changing internal state.
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                Author and article information

                Contributors
                daniela.popa@bio.ens.psl.eu
                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group UK (London )
                2041-1723
                15 October 2020
                15 October 2020
                2020
                : 11
                : 5207
                Affiliations
                GRID grid.4444.0, ISNI 0000 0001 2112 9282, Neurophysiology of Brain Circuits Team, Institut de Biologie de l’Ecole normale supérieure (IBENS), Ecole normale supérieure, CNRS, INSERM, PSL Research University, ; 75005 Paris, France
                Author information
                http://orcid.org/0000-0003-2175-5739
                http://orcid.org/0000-0002-8389-1122
                Article
                18953
                10.1038/s41467-020-18953-0
                7566591
                33060630
                be4da7b3-bb90-4275-8a48-0d0c115a154b
                © 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
                : 13 December 2019
                : 17 September 2020
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100007700, Universitatea de Medicină şi Farmacie "Carol Davila" Bucureşti (Carol Davila University of Medicine and Pharmacy);
                Award ID: 819/11.01.2019
                Award Recipient :
                Funded by: FundRef https://doi.org/10.13039/501100001665, Agence Nationale de la Recherche (French National Research Agency);
                Award ID: ANR-17-CE37-0009
                Award ID: ANR-17-CE16-0019
                Award ID: ANR-19-CE37-0007-01
                Award ID: ANR-16-CE37-0003-02
                Award Recipient :
                Categories
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                © The Author(s) 2020

                Uncategorized
                emotion,neural circuits
                Uncategorized
                emotion, neural circuits

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