45 research outputs found

    Genetic Activation, Inactivation, and Deletion Reveal a Limited And Nuanced Role for Somatostatin-Containing Basal Forebrain Neurons in Behavioral State Control

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    Recent studies have identified an especially important role for basal forebrain GABAergic (BF(VGAT)) neurons in the regulation of behavioral waking and fast cortical rhythms associated with cognition. However, BF(VGAT) neurons comprise several neurochemically and anatomically distinct subpopulations, including parvalbumin-containing BF(VGAT) neurons and somatostatin-containing BF(VGAT) neurons (BF(SOM) neurons), and it was recently reported that optogenetic activation of BF(SOM) neurons increases the probability of a wakefulness to non-rapid-eye movement (NREM) sleep transition when stimulated during the rest period of the animal. This finding was unexpected given that most BF(SOM) neurons are not NREM sleep active and that central administration of the synthetic somatostatin analog, octreotide, suppresses NREM sleep or increases REM sleep. Here we used a combination of genetically driven chemogenetic and optogenetic activation, chemogenetic inhibition, and ablation approaches to further explore the in vivo role of BF(SOM) neurons in arousal control. Our findings indicate that acute activation or inhibition of BF(SOM) neurons is neither wakefulness nor NREM sleep promoting and is without significant effect on the EEG, and that chronic loss of these neurons is without effect on total 24 h sleep amounts, although a small but significant increase in waking was observed in the lesioned mice during the early active period. Our in vitro cell recordings further reveal electrophysiological heterogeneity in BF(SOM) neurons, specifically suggesting at least two distinct subpopulations. Together, our data support the more nuanced view that BF(SOM) neurons are electrically heterogeneous and are not NREM sleep or wake promoting per se, but may exert, in particular during the early active period, a modest inhibitory influence on arousal circuitry.SIGNIFICANCE STATEMENT The cellular basal forebrain (BF) is a highly complex area of the brain that is implicated in a wide range of higher-level neurobiological processes, including regulating and maintaining normal levels of electrocortical and behavioral arousal. The respective in vivo roles of BF cell populations and their neurotransmitter systems in the regulation of electrocortical and behavioral arousal remains incompletely understood. Here we seek to define the neurobiological contribution of GABAergic somatostatin-containing BF neurons to arousal control. Understanding the respective contribution of BF cell populations to arousal control may provide critical insight into the pathogenesis of a host of neuropsychiatric and neurodegenerative disorders, including Alzheimer\u27s disease, Parkinson\u27s disease, schizophrenia, and the cognitive impairments of normal aging

    Suprachiasmatic VIP neurons are required for normal circadian rhythmicity and comprised of molecularly distinct subpopulations

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    The hypothalamic suprachiasmatic (SCN) clock contains several neurochemically defined cell groups that contribute to the genesis of circadian rhythms. Using cell-specific and genetically targeted approaches we have confirmed an indispensable role for vasoactive intestinal polypeptide-expressing SCN (SCN(VIP)) neurons, including their molecular clock, in generating the mammalian locomotor activity (LMA) circadian rhythm. Optogenetic-assisted circuit mapping revealed functional, di-synaptic connectivity between SCN(VIP) neurons and dorsomedial hypothalamic neurons, providing a circuit substrate by which SCN(VIP) neurons may regulate LMA rhythms. In vivo photometry revealed that while SCN(VIP) neurons are acutely responsive to light, their activity is otherwise behavioral state invariant. Single-nuclei RNA-sequencing revealed that SCN(VIP) neurons comprise two transcriptionally distinct subtypes, including putative pacemaker and non-pacemaker populations. Altogether, our work establishes necessity of SCN(VIP) neurons for the LMA circadian rhythm, elucidates organization of circadian outflow from and modulatory input to SCN(VIP) cells, and demonstrates a subpopulation-level molecular heterogeneity that suggests distinct functions for specific SCN(VIP) subtypes

    Supramammillary glutamate neurons are a key node of the arousal system

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    Basic and clinical observations suggest that the caudal hypothalamus comprises a key node of the ascending arousal system, but the cell types underlying this are not fully understood. Here we report that glutamate-releasing neurons of the supramammillary region (SuMvglut2) produce sustained behavioral and EEG arousal when chemogenetically activated. This effect is nearly abolished following selective genetic disruption of glutamate release from SuMvglut2 neurons. Inhibition of SuMvglut2 neurons decreases and fragments wake, also suppressing theta and gamma frequency EEG activity. SuMvglut2 neurons include a subpopulation containing both glutamate and GABA (SuMvgat/vglut2) and another also expressing nitric oxide synthase (SuMNos1/Vglut2). Activation of SuMvgat/vglut2 neurons produces minimal wake and optogenetic stimulation of SuMvgat/vglut2 terminals elicits monosynaptic release of both glutamate and GABA onto dentate granule cells. Activation of SuMNos1/Vglut2 neurons potently drives wakefulness, whereas inhibition reduces REM sleep theta activity. These results identify SuMvglut2 neurons as a key node of the wake−sleep regulatory system

    A simple deterministic plastoelastohydrodynamic lubrication (PEHL) model in mixed lubrication

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    Most power transmitting components operate under mixed lubrication conditions. Concentrated pressures and smaller lubricant film thickness may cause surface and subsurface stresses to exceed the material yield limit causing permanent geometrical changes. A model was developed to include elastoplastic behaviour within a deterministic unified mixed lubrication framework. Model details are presented and the model is validated against published simulation data. A parametric study to address the effect of material yielding on the contact parameters is performed. It is found that the model successfully produces all the key features of the PEHL contact. The model provides a valuable tool to analyse the PEHL contacts with minimal increase in computational effort and complexity

    40 juegos para la expresión corporal : de 3 a 10 años

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    Se centra en la expresión corporal para los diferentes niveles de alumnado de la escuela. La expresión corporal se sitúa en el eje de diferentes áreas: danza, expresión dramática, teatro, relajación... Para desarrollar dicha expresión, se presentan 40 juegos que proponen aproximaciones al movimiento, tacto, sentidos... Incitados y educados por la escenificación de temas variados, desarrollados por los mismos niños en un marco espacial y temporal definido por el maestro.CataluñaBiblioteca de Educación del Ministerio de Educación, Cultura y Deporte; Calle San Agustín 5 -3 Planta; 28014 Madrid; Tel. +34917748000; [email protected]

    Bart and Anne Venner: forestry manager & nurse

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    Bart worked in the Forest of Dean as Assistant Forester, later taking responsibility for establishing and running Forest of Dean campsites and, later, in charge of timber contracts. Towards the end of his career Bart was placed in charge of dealings with private woodlands in the area. Anne worked for several years at The Dilke Hospital, later working for Marie Curie, caring for those with terminal illnesses. This oral history is part of the Voices from the Forest series uncovering the working lives of people in the Forest landscape. Overview: The ‘Voices from the Forest’ collection represents a series of oral history recordings made between 2016 and 2019 (continuing) and funded as part of the Foresters’ Forest project, a National Lottery Heritage Fund landscape partnership programme. The recordings take a biographical, life story approach to discover the occupational histories of men and women in the Forest of Dean in the last half of the twentieth century. It compliments a series of recordings, made in the 1980s by Elsie O’Livey in the Forest of Dean, that feature the life stories of people in the first half of the century. The recordings are a rich source of material for social geographers, social and cultural historians and those interested in the history of the Forest of Dean and the broad occupational history of the area. The recordings feature recollections of men who worked thorough the last days of large-scale coal mining in the area, forestry related work and their adaptation to new modes of employment in fabrication and manufacturing industries. The collection has made a special emphasis on recording the experiences of women in the domestic setting, their experiences in the factories that grew throughout the period and the diaspora providing domestic services in London, Cheltenham and elsewhere. The improvements in domestic utilities, education and opportunity are reflected across the recordings. The recordings also reflect the economic uncertainty that existed throughout the twentieth century and the persistence of traditional activities such as sheep commoning, freemining and small holding that provided alternative forms of sustainable family living. The experience of major events such as the Second World War, post war rationing, and the Foot and Mouth epidemics are covered. The recordings were made in the homes of the interviewees and consents and permissions were in accordance with GDPR (2019)

    A propos des jeux paradoxaux

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