Illuminating Neuronal-Astrocytic Pathways for Sleep homeostasis

Información del proyecto

iNAPS

Identificador del acuerdo de subvención: 715933

DOI

10.3030/715933

Proyecto cerrado

Fecha de la firma de la CE 16 Diciembre 2016

Fecha de inicio 1 Abril 2017

Fecha de finalización 31 Marzo 2023

Financiado con arreglo a

• EXCELLENT SCIENCE - European Research Council (ERC)

Coste total

€ 1 500 000,00

Aportación de la UE

€ 1 500 000,00

Coordinado por

HELMHOLTZ ZENTRUM MUENCHEN DEUTSCHES FORSCHUNGSZENTRUM FUER GESUNDHEIT UND UMWELT GMBH
Germany

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

Período documentado: 2021-10-01 hasta 2023-03-31

Resumen del contexto y de los objetivos generales del proyecto

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.

Trabajo realizado desde el comienzo del proyecto hasta el final del período abarcado por el informe y los principales resultados hasta la fecha

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.

Avances que van más allá del estado de la técnica e impacto potencial esperado (incluida la repercusión socioeconómica y las implicaciones sociales más amplias del proyecto hasta la fecha)

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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