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iNAPS SIGNED

Illuminating Neuronal-Astrocytic Pathways for Sleep homeostasis

Total Cost €

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EC-Contrib. €

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Partnership

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 iNAPS project word cloud

Explore the words cloud of the iNAPS project. It provides you a very rough idea of what is the project "iNAPS" about.

adaptive    question    safeguard    machinery    rebound    homeostasis    functional    astrocyte    brain    regenerative    unclear    discovered    building    shed    pervasive    hypothesise    release    fundamental    consolidated    intensified    imaging    translates    rbs    generation    interneurons    network    decode    neurokinin    interactions    form    profiles    cortical    pressure    health    expressing    productivity    sd    inadequate    superior    foundation    function    delayed    unusual    caused    group    astrocytes    phosphorylated    knockout    nk1    restorative    mice    impairs    sleep    activation    synthase    mechanisms    remarkable    neurons    society    homeostatically    sensitive    newly    urgently    nitric    understand    light    vivo    astrocytic    nnos    therapeutic    deprivation    follows    ribosome    aids    found    transcriptomic    receptor    activated    play    ado    neuronal    enigmatic    profiling    severely    messenger    manipulation    excitatory    adenosinergic    chemogenetic    oxide    senses    adenosine    selectively    verify   

Project "iNAPS" data sheet

The following table provides information about the project.

Coordinator
HELMHOLTZ ZENTRUM MUENCHEN DEUTSCHES FORSCHUNGSZENTRUM FUER GESUNDHEIT UND UMWELT GMBH 

Organization address
address: INGOLSTADTER LANDSTRASSE 1
city: NEUHERBERG
postcode: 85764
website: www.helmholtz-muenchen.de

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Germany [DE]
 Total cost 1˙500˙000 €
 EC max contribution 1˙500˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2016-STG
 Funding Scheme ERC-STG
 Starting year 2017
 Duration (year-month-day) from 2017-04-01   to  2022-03-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    HELMHOLTZ ZENTRUM MUENCHEN DEUTSCHES FORSCHUNGSZENTRUM FUER GESUNDHEIT UND UMWELT GMBH DE (NEUHERBERG) coordinator 1˙500˙000.00

Map

 Project objective

Sleep is crucial to the brain’s remarkable regenerative and adaptive capabilities. Inadequate sleep is a pervasive problem that severely impairs brain function, productivity, and health. How the brain homeostatically senses sleep need and translates it into the intensified rebound sleep (RBS) that follows sleep deprivation (SD) still remains unclear. I aim to understand these mechanisms and to identify therapeutic targets that will promote consolidated, restorative sleep, enabling the development of superior sleep aids. Furthermore, this will shed light on the enigmatic yet fundamental question of the function of sleep. Astrocyte activation increases sleep, and astrocytes release adenosine (ado), a key messenger for sleep homeostasis. Thus, astrocytic-neuronal interactions likely decode sleep pressure into RBS via adenosinergic mechanisms. I discovered that cortical interneurons expressing neuronal nitric oxide synthase (nNOS) and neurokinin-1 receptor (NK1), which are selectively activated in RBS, show highly unusual excitatory responses to ado that are sensitive to sleep pressure. Furthermore, I found that knockout of a specific ado receptor in mice caused reduced numbers of cortical nNOS/NK1 neurons as well as a delayed RBS response. Based on these findings, I hypothesise that cortical nNOS/NK1 neurons play a key role in sleep homeostasis. My group now aims to 1) identify the comprehensive sleep homeostasis machinery, by building transcriptomic profiles of neurons activated during and after SD in mice using phosphorylated ribosome profiling, 2) verify the function of these newly identified neurons in sleep homeostasis by activity imaging and chemogenetic manipulation in vivo, and 3) investigate the functional role of astrocytes in the sleep homeostasis network. These studies will form the foundation for a new generation of sleep aids that are urgently needed to safeguard the productivity and health of our society.

 Publications

year authors and title journal last update
List of publications.
2017 Rhîannan H Williams, Jacqueline Vazquez-DeRose, Alexia M Thomas, Juliette Piquet, Bruno Cauli, Thomas S Kilduff
Cortical nNOS/NK1 Receptor Neurons are Regulated by Cholinergic Projections From the Basal Forebrain
published pages: 1959-1979, ISSN: 1047-3211, DOI: 10.1093/cercor/bhx102
Cerebral Cortex 28/6 2019-12-16
2019 Rhîannan H. Williams, Tomomi Tsunematsu, Alexia M. Thomas, Kelsie Bogyo, Akihiro Yamanaka, Thomas S. Kilduff
Transgenic Archaerhodopsin-3 Expression in Hypocretin/Orexin Neurons Engenders Cellular Dysfunction and Features of Type 2 Narcolepsy
published pages: 9435-9452, ISSN: 0270-6474, DOI: 10.1523/jneurosci.0311-19.2019
The Journal of Neuroscience 39/47 2019-12-16
2018 Rhîannan H Williams, Sarah W Black, Alexia M Thomas, Juliette Piquet, Bruno Cauli, Thomas S Kilduff
Excitation of Cortical nNOS/NK1R Neurons by Hypocretin 1 is Independent of Sleep Homeostasis
published pages: 1090-1108, ISSN: 1047-3211, DOI: 10.1093/cercor/bhy015
Cerebral Cortex 29/3 2019-12-16

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