Obiettivo 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. Campo scientifico medical and health scienceshealth sciencesinfectious diseasesRNA virusesHIVsocial scienceseconomics and businesseconomicsproduction economicsproductivitymedical and health sciencesbasic medicinephysiologyhomeostasis Programma(i) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Argomento(i) ERC-2016-STG - ERC Starting Grant Invito a presentare proposte ERC-2016-STG Vedi altri progetti per questo bando Meccanismo di finanziamento ERC-STG - Starting Grant Istituzione ospitante HELMHOLTZ ZENTRUM MUENCHEN DEUTSCHES FORSCHUNGSZENTRUM FUER GESUNDHEIT UND UMWELT GMBH Contribution nette de l'UE € 1 500 000,00 Indirizzo INGOLSTADTER LANDSTRASSE 1 85764 Neuherberg Germania Mostra sulla mappa Regione Bayern Oberbayern München, Landkreis Tipo di attività Research Organisations Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Partecipazione a programmi di R&I dell'UE Opens in new window Rete di collaborazione HORIZON Opens in new window Costo totale € 1 500 000,00 Beneficiari (1) Classifica in ordine alfabetico Classifica per Contributo netto dell'UE Espandi tutto Riduci tutto HELMHOLTZ ZENTRUM MUENCHEN DEUTSCHES FORSCHUNGSZENTRUM FUER GESUNDHEIT UND UMWELT GMBH Germania Contribution nette de l'UE € 1 500 000,00 Indirizzo INGOLSTADTER LANDSTRASSE 1 85764 Neuherberg Mostra sulla mappa Regione Bayern Oberbayern München, Landkreis Tipo di attività Research Organisations Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Partecipazione a programmi di R&I dell'UE Opens in new window Rete di collaborazione HORIZON Opens in new window Costo totale € 1 500 000,00
