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      Paraventricular hypothalamic vasopressin neurons induce self-grooming in mice

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          Abstract

          Self-grooming plays an essential role in hygiene maintenance, thermoregulation, and stress response. However, the neural populations involved in self-grooming remain largely unknown. The paraventricular hypothalamic nucleus (PVH) has been implicated in the regulation of self-grooming. Arginine vasopressin-producing neurons are among the major neuronal populations in the PVH (PVH AVP), which play important roles in water homeostasis, blood pressure regulation, feeding, and stress response. Here, we report the critical role of PVH AVP neurons in the induction of self-grooming. Optogenetic activation of PVH AVP neurons immediately induced self-grooming in freely moving mice. Chemogenetic activation of these neurons also increased time spent self-grooming. In contrast, their chemogenetic inhibition significantly reduced naturally occurring self-grooming, suggesting that PVH AVP-induced grooming has physiological relevance. Notably, optogenetic activation of PVH AVP neurons triggered self-grooming over other adaptive behaviors, such as voracious feeding induced by fasting and social interaction with female mice. Thus, our study proposes the novel role of PVH AVP neurons in regulating self-grooming behavior and, consequently, hygiene maintenance and stress response. Furthermore, uncontrolled activation of these neurons may be potentially relevant to diseases characterized by compulsive behaviors and impaired social interaction, such as autism, obsessive–compulsive disorder, and anorexia nervosa.

          Supplementary Information

          The online version contains supplementary material available at 10.1186/s13041-022-00932-9.

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          Most cited references50

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          Double-slit photoelectron interference in strong-field ionization of the neon dimer

          Wave-particle duality is an inherent peculiarity of the quantum world. The double-slit experiment has been frequently used for understanding different aspects of this fundamental concept. The occurrence of interference rests on the lack of which-way information and on the absence of decoherence mechanisms, which could scramble the wave fronts. Here, we report on the observation of two-center interference in the molecular-frame photoelectron momentum distribution upon ionization of the neon dimer by a strong laser field. Postselection of ions, which are measured in coincidence with electrons, allows choosing the symmetry of the residual ion, leading to observation of both, gerade and ungerade, types of interference.
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            U1 snRNP regulates cancer cell migration and invasion in vitro

            Stimulated cells and cancer cells have widespread shortening of mRNA 3’-untranslated regions (3’UTRs) and switches to shorter mRNA isoforms due to usage of more proximal polyadenylation signals (PASs) in introns and last exons. U1 snRNP (U1), vertebrates’ most abundant non-coding (spliceosomal) small nuclear RNA, silences proximal PASs and its inhibition with antisense morpholino oligonucleotides (U1 AMO) triggers widespread premature transcription termination and mRNA shortening. Here we show that low U1 AMO doses increase cancer cells’ migration and invasion in vitro by up to 500%, whereas U1 over-expression has the opposite effect. In addition to 3’UTR length, numerous transcriptome changes that could contribute to this phenotype are observed, including alternative splicing, and mRNA expression levels of proto-oncogenes and tumor suppressors. These findings reveal an unexpected role for U1 homeostasis (available U1 relative to transcription) in oncogenic and activated cell states, and suggest U1 as a potential target for their modulation.
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              Neocortical excitation/inhibition balance in information processing and social dysfunction.

              Severe behavioural deficits in psychiatric diseases such as autism and schizophrenia have been hypothesized to arise from elevations in the cellular balance of excitation and inhibition (E/I balance) within neural microcircuitry. This hypothesis could unify diverse streams of pathophysiological and genetic evidence, but has not been susceptible to direct testing. Here we design and use several novel optogenetic tools to causally investigate the cellular E/I balance hypothesis in freely moving mammals, and explore the associated circuit physiology. Elevation, but not reduction, of cellular E/I balance within the mouse medial prefrontal cortex was found to elicit a profound impairment in cellular information processing, associated with specific behavioural impairments and increased high-frequency power in the 30-80 Hz range, which have both been observed in clinical conditions in humans. Consistent with the E/I balance hypothesis, compensatory elevation of inhibitory cell excitability partially rescued social deficits caused by E/I balance elevation. These results provide support for the elevated cellular E/I balance hypothesis of severe neuropsychiatric disease-related symptoms.
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                Author and article information

                Contributors
                tarikul2042@stu.kanazawa-u.ac.jp
                tmaejima@med.kanazawa-u.ac.jp
                matsuia@med.kanazawa-u.ac.jp
                mieda@med.kanazawa-u.ac.jp
                Journal
                Mol Brain
                Mol Brain
                Molecular Brain
                BioMed Central (London )
                1756-6606
                23 May 2022
                23 May 2022
                2022
                : 15
                : 47
                Affiliations
                GRID grid.9707.9, ISNI 0000 0001 2308 3329, Department of Integrative Neurophysiology, Graduate School of Medical Sciences, , Kanazawa University, ; 13-1 Takara-machi, Kanazawa, Ishikawa 920-8640 Japan
                Author information
                https://orcid.org/0000-0003-2822-245X
                https://orcid.org/0000-0002-0490-2701
                http://orcid.org/0000-0002-2451-7034
                Article
                932
                10.1186/s13041-022-00932-9
                9125887
                35606816
                7c8f7f4a-d321-43ae-9e4e-606136557e6f
                © The Author(s) 2022

                Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 24 March 2022
                : 9 May 2022
                Funding
                Funded by: MEXT/JSPS KAKENHI
                Award ID: JP16H05120
                Award ID: JP19H03399
                Award ID: JP20K21498
                Award ID: JP18K06519
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100007449, Takeda Science Foundation;
                Funded by: FundRef http://dx.doi.org/10.13039/100007428, Naito Foundation;
                Funded by: FundRef http://dx.doi.org/10.13039/501100005927, Daiichi Sankyo Foundation of Life Science;
                Funded by: Kao Research Council for the Study of Healthcare Science
                Funded by: Kanazawa University CHOZEN project
                Funded by: MEXT Japanese Government Scholarship for International Students
                Categories
                Research
                Custom metadata
                © The Author(s) 2022

                Neurosciences
                self-grooming,vasopressin,paraventricular hypothalamic nucleus,channelrhodopsin,dreadds,repetitive behavior

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