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dc.contributor.author Autor Mondino, Alejandra-
dc.contributor.author Autor Hambrecht-Wiedbusch, Viviane S.-
dc.contributor.author Autor Li, Duan-
dc.contributor.author Autor York, A. Kane-
dc.contributor.author Autor Pal, Dinesh-
dc.contributor.author Autor González, Joaquín-
dc.contributor.author Autor Torterolo, Pablo-
dc.contributor.author Autor Mashour, George A.-
dc.contributor.author Autor Vanini, Giancarlo-
dc.contributor.filiacion Filiación Mondino Alejandra, Universidad de la República (Uruguay). Facultad de Medicina. Departamento de Fisiología; University of Michigan (E.E.U.U.). Department of Anesthesiology and Center for Consciousness Science-
dc.contributor.filiacion Filiación Hambrecht-Wiedbusch Viviane S., University of Michigan (E.E.U.U.). Department of Anesthesiology and Center for Consciousness Science-
dc.contributor.filiacion Filiación Li Duan, University of Michigan (E.E.U.U.). Department of Anesthesiology and Center for Consciousness Science-
dc.contributor.filiacion Filiación York A. Kane, University of Michigan (E.E.U.U.). Department of Anesthesiology and Neuroscience Graduate Program-
dc.contributor.filiacion Filiación Pal Dinesh, University of Michigan (E.E.U.U.). Department of Anesthesiology, Center for Consciousness Science and Neuroscience Graduate Program-
dc.contributor.filiacion Filiación González Joaquín, Universidad de la República (Uruguay). Facultad de Medicina. Departamento de Fisiología-
dc.contributor.filiacion Filiación Torterolo Pablo, Universidad de la República (Uruguay). Facultad de Medicina. Departamento de Fisiología-
dc.contributor.filiacion Filiación Mashour George A., University of Michigan (E.E.U.U.). Department of Anesthesiology, Center for Consciousness Science and Neuroscience Graduate Program-
dc.contributor.filiacion Filiación Vanini Giancarlo, University of Michigan (E.E.U.U.). Department of Anesthesiology, Center for Consciousness Science and Neuroscience Graduate Program-
dc.date.accessioned Fecha ingreso 2026-06-12T16:41:15Z-
dc.date.available Fecha disponible 2026-06-12T16:41:15Z-
dc.date.issued Año de publicación 2021-
dc.description.abstract Resumen Clinical and experimental data from the last nine decades indicate that the preoptic area of the hypothalamus is a critical node in a brain network that controls sleep onset and homeostasis. By contrast, we recently reported that a group of glutamatergic neurons in the lateral and medial preoptic area increases wakefulness, challenging the long-standing notion in sleep neurobiology that the preoptic area is exclusively somnogenic. However, the precise role of these subcortical neurons in the control of behavioral state transitions and cortical dynamics remains unknown. Therefore, in this study, we used conditional expression of excitatory hM3Dq receptors in these preoptic glutamatergic (Vglut2+) neurons and show that their activation initiates wakefulness, decreases non-rapid eye movement (NREM) sleep, and causes a persistent suppression of rapid eye movement (REM) sleep. We also demonstrate, for the first time, that activation of these preoptic glutamatergic neurons causes a high degree of NREM sleep fragmentation, promotes state instability with frequent arousals from sleep, decreases body temperature, and shifts cortical dynamics (including oscillations, connectivity, and complexity) to a more wake-like state. We conclude that a subset of preoptic glutamatergic neurons can initiate, but not maintain, arousals from sleep, and their inactivation may be required for NREM stability and REM sleep generation. Further, these data provide novel empirical evidence supporting the hypothesis that the preoptic area causally contributes to the regulation of both sleep and wakefulness.SIGNIFICANCE STATEMENT Historically, the preoptic area of the hypothalamus has been considered a key site for sleep generation. However, emerging modeling and empirical data suggest that this region might play a dual role in sleep-wake control. We demonstrate that chemogenetic stimulation of preoptic glutamatergic neurons produces brief arousals that fragment sleep, persistently suppresses REM sleep, causes hypothermia, and shifts EEG patterns toward a "lighter" NREM sleep state. We propose that preoptic glutamatergic neurons can initiate, but not maintain, arousal from sleep and gate REM sleep generation, possibly to block REM-like intrusions during NREM-to-wake transitions. In contrast to the long-standing notion in sleep neurobiology that the preoptic area is exclusively somnogenic, we provide further evidence that preoptic neurons also generate wakefulness.es
dc.format.extent Extensión 17 p.es
dc.format.mimetype Formato application/pdfes
dc.identifier.citation Citación Mondino A, Hambrecht-Wiedbusch V, Li D y otros. Glutamatergic Neurons in the Preoptic Hypothalamus Promote Wakefulness, Destabilize NREM Sleep, Suppress REM Sleep, and Regulate Cortical Dynamics. The Journal of Neuroscience [en línea]. 2021;41(15):3462-3478es
dc.identifier.doi DOI 10.1523/JNEUROSCI.2718-20.2021-
dc.identifier.eissn e-ISSN 1529-2401-
dc.identifier.uri URI https://hdl.handle.net/20.500.12008/55495-
dc.language.iso Idioma enes
dc.publisher Editorial Society for Neurosciencees
dc.relation.ispartof EN The Journal of Neuroscience. 2021;41(15):3462-3478es
dc.rights Derechos Las obras depositadas en el Repositorio se rigen por la Ordenanza de los Derechos de la Propiedad Intelectual de la Universidad de la República.(Res. Nº 91 de C.D.C. de 8/III/1994 – D.O. 7/IV/1994) y por la Ordenanza del Repositorio Abierto de la Universidad de la República (Res. Nº 16 de C.D.C. de 07/10/2014)es
dc.rights.licence Licencia Licencia Creative Commons Atribución (CC - By 4.0)es
dc.subject Palabras clave DREADDses
dc.subject Palabras clave Arousales
dc.subject Palabras clave Consciousnesses
dc.subject Palabras clave Gammaes
dc.subject Palabras clave Sleep fragmentationes
dc.subject Palabras clave Slow oscillationses
dc.subject.other Descriptores ANIMALESes
dc.subject.other Descriptores ONDAS ENCEFÁLICASes
dc.subject.other Descriptores ÁCIDO GLUTÁMICOes
dc.subject.other Descriptores METABOLISMOes
dc.subject.other Descriptores HIPOTÁLAMOes
dc.subject.other Descriptores CITOLOGÍAes
dc.subject.other Descriptores RATONESes
dc.subject.other Descriptores FISIOLOGÍAes
dc.subject.other Descriptores NEURONASes
dc.subject.other Descriptores SUEÑO REMes
dc.subject.other Descriptores PROTEÍNA 2 DE TRANSPORTE VESICULAR DE GLUTAMATOes
dc.subject.other Descriptores GENÉTICAes
dc.subject.other Descriptores VIGILIAes
dc.subject.other Descriptores MASCULINOes
dc.title Título Glutamatergic Neurons in the Preoptic Hypothalamus Promote Wakefulness, Destabilize NREM Sleep, Suppress REM Sleep, and Regulate Cortical Dynamicses
dc.type Tipo de documento Artículoes

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