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Author Notes:

Correspondence and requests for materials should be addressed to N.P.P. (email: npeders@emory.edu) or to P.M.F. (email: pfuller@bidmc.harvard.edu)

Clifford B. Saper and Patrick M. Fuller contributed equally to this work.

N.P.P., N.V., E.A., P.M.F. and C.B.S. were responsible for study inception and design of experiments.

N.P.P., L.F., J.L.W., A.V., S.B.A., E.A. and P.M.F. performed experiments.

N.P.P., L.F., J.L.W., A.V., S.B.A., E.A., P.M.F. and C.B.S. analyzed or interpreted data.

N.P.P., E.A., P.M.F. and C.B.S. wrote the paper.

We are grateful for the technical assistance of Quan Hue Ha, Minh Ha, Sarah Keating, Myriam Debryune, and Rebecca Broadhurst, and for the kind gift, from Drs Bradford Lowell and Linh Vong, of Vgat-IRES-cre and Vglut2-IRES-cre lines of mice.

The authors declare no competing financial interests.

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Subjects:

Research Funding:

This work was supported by the National Institutes of Health R25NS070682 and an American Academy of Neurology and American Brain Foundation Clinician-Researcher Training Fellowship (N.P.P.), as well as NARSAD Young Investigator Grant (A.V.), National Health and Medical Research Council of Australia Early Career Fellowship GNT1052674 (S.B.G.A.).

National Health and Medical Research Council C.J. Martin Award (S.B.G.A.), National Institutes of Health grants R21NS082854 (E.A.), R01NS073613 (P.M.F.), R01NS092652 (P.M.F.), R01NS085477 (C.B.S.), and P01HL095491 (C.B.S., E.A.).

Keywords:

  • Science & Technology
  • Multidisciplinary Sciences
  • Science & Technology - Other Topics
  • AQUAPORIN 4 ANTIBODY
  • SYMMETRICAL HYPOTHALAMIC-LESIONS
  • NITRIC-OXIDE SYNTHASE
  • BASAL FOREBRAIN
  • REVERSIBLE INACTIVATION
  • POSTERIOR HYPOTHALAMUS
  • SUBSTANTIA INNOMINATA
  • GABAERGIC NEURONS
  • LEPTIN ACTION
  • PHA-L

Supramammillary glutamate neurons are a key node of the arousal system

Journal Title:

Nature Communications

Volume:

Volume 8, Number 1

Publisher:

, Pages 1405-1405

Type of Work:

Article | Final Publisher PDF

Abstract:

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 (SuM vglut2 ) produce sustained behavioral and EEG arousal when chemogenetically activated. This effect is nearly abolished following selective genetic disruption of glutamate release from SuM vglut2 neurons. Inhibition of SuM vglut2 neurons decreases and fragments wake, also suppressing theta and gamma frequency EEG activity. SuM vglut2 neurons include a subpopulation containing both glutamate and GABA (SuM vgat/vglut2 ) and another also expressing nitric oxide synthase (SuM Nos1/Vglut2 ). Activation of SuM vgat/vglut2 neurons produces minimal wake and optogenetic stimulation of SuM vgat/vglut2 terminals elicits monosynaptic release of both glutamate and GABA onto dentate granule cells. Activation of SuM Nos1/Vglut2 neurons potently drives wakefulness, whereas inhibition reduces REM sleep theta activity. These results identify SuM vglut2 neurons as a key node of the wake-sleep regulatory system.

Copyright information:

© 2017 The Author(s).

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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