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Illuminating Neuronal-Astrocytic Pathways for Sleep homeostasis

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.

Field of science

  • /medical and health sciences/basic medicine/physiology/homeostasis
  • /medical and health sciences/health sciences/infectious disease/RNA virus/hiv
  • /social sciences/economics and business/economics/production economics/productivity

Call for proposal

ERC-2016-STG
See other projects for this call

Funding Scheme

ERC-STG - Starting Grant

Host institution

HELMHOLTZ ZENTRUM MUENCHEN DEUTSCHES FORSCHUNGSZENTRUM FUER GESUNDHEIT UND UMWELT GMBH
Address
Ingolstadter Landstrasse 1
85764 Neuherberg
Germany
Activity type
Research Organisations
EU contribution
€ 1 500 000

Beneficiaries (1)

HELMHOLTZ ZENTRUM MUENCHEN DEUTSCHES FORSCHUNGSZENTRUM FUER GESUNDHEIT UND UMWELT GMBH
Germany
EU contribution
€ 1 500 000
Address
Ingolstadter Landstrasse 1
85764 Neuherberg
Activity type
Research Organisations