Illuminating Neuronal-Astrocytic Pathways for Sleep homeostasis

Informazioni relative al progetto

iNAPS

ID dell’accordo di sovvenzione: 715933

DOI

10.3030/715933

Progetto chiuso

Data della firma CE 16 Dicembre 2016

Data di avvio 1 Aprile 2017

Data di completamento 31 Marzo 2023

Finanziato da

• EXCELLENT SCIENCE - European Research Council (ERC)

Costo totale

€ 1 500 000,00

Contributo UE

€ 1 500 000,00

Coordinato da

HELMHOLTZ ZENTRUM MUENCHEN DEUTSCHES FORSCHUNGSZENTRUM FUER GESUNDHEIT UND UMWELT GMBH
Germany

Periodic Reporting for period 4 - iNAPS (Illuminating Neuronal-Astrocytic Pathways for Sleep homeostasis)

Periodo di rendicontazione: 2021-10-01 al 2023-03-31

Sintesi del contesto e degli obiettivi generali del progetto

ERC iNAPS 715933 aimed to discern the mechanisms controlling sleep homeostasis. In other words, to understand how the brain senses the need for sleep and drives appropriate sleep patterns. Most people know what sleep deprivation feels like, yet the impact of significant sleep loss on health, safety, and the economy is underappreciated. We believe that if we can understand the brain circuits functioning in sleep deprivation and governing sleep drive, we can devise ways to augment them, enabling more restorative sleep and all the beneficial health, safety, and economic benefits that ensue.

The overall objectives were: 1) identify the cell types and brain regions involved in sleep homeostasis; 2) determine how these cells affect sleep drive; and 3) evaluate the role of astrocytes, a special type of brain cell, in sleep homeostasis.
In the course of the action, we achieved the main objectives, gaining understanding of the cellular basis of sleep homeostasis and laying the foundation for future work in this area.

Lavoro eseguito dall’inizio del progetto fino alla fine del periodo coperto dalla relazione e principali risultati finora ottenuti

We Identified a molecularly defined population of neurons in the brain’s amygdala, a region often associated with emotion, that are activated by sleep deprivation. We manipulated their activity to reveal that these cells are important in driving recovery sleep to regain sleep homeostasis. We concluded that these cells are not critical for normal sleep-wake state regulation, since 1) activating these cells promotes sleep irrespective of low sleep, and 2) there is no effect of inhibiting these cells when normal sleep-wake patterns occur. In conclusion, we successfully identified and characterized a new cellular population involved in sleep homeostasis.

We also identified that a population of non-neuronal cells called astrocytes in the brain’s cortex that are sensitive to changes in sleep pressure. With sleep loss, we found altered protein expression in these cells. Furthermore, we found that activation of these astrocytes in the cortex promoted sleep onset, but only after sleep deprivation. In conclusion, we gained significant understanding of the role of astrocytes in sleep homeostasis.

Theses results have bene presented in part at international conferences. The resulting manuscripts which report these scientific advances are in preparation. As there is no current funding to cover publication submission fees, we aim to deposit these results in an online archive for dissemination to the research community.

Progressi oltre lo stato dell’arte e potenziale impatto previsto (incluso l’impatto socioeconomico e le implicazioni sociali più ampie del progetto fino ad ora)

We created an unprecedented brain-wide map of cellular activity under conditions of sleep deprivation and recovery sleep, leading to the identification of a previously unknown population of cells activated by sleep deprivation in the amygdala. For the first time, we were able to gain specific pharmacological access to these cells to switch them on and off and observe the effects on sleep, leading to understanding of their role in sleep regulation. Finally, for the first time, we demonstrated changes in the shape of astrocytes, as marked by the expression of a protein, with sleep deprivation.

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