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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.

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

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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