Objectif Sleep and anaesthesia are both commonplace states that involve reversible loss of consciousness. However, the precise regulatory mechanisms underlying both still remain elusive, particularly at the circuitry level. Previous studies suggest that sleep is homeostatically regulated and it has been proposed that the interaction between circadian rhythm and intrinsic sleep drive determines sleep status. Although much efforts have been made, the sleep field still lacks clarity regarding the nature of the “sleep drive” as well as how it modulates sleep homeostasis. My host lab recently revealed that neuronal ensembles in the PO area, particularly in the lateral PO (LPO) area, a small region at the base of the brain that contains a mixture of sleep-active, wake-active, and temperature-sensitive neurons, are selectively activated during recovery sleep and drug-induced sedation. These results indicate that the LPO neurons are able to sense the sleep drive. In this proposal my goal is to identify LPO associated functional connectivity encoding sleep drive and sedation. By combining TetTagging functional ensembles of neurons with in vitro and in vivo optogenetics, electrophysiology and imaging techniques in mouse, I aim to 1) evaluate alterations of excitatory/inhibitory inputs onto the defined LPO neurons during prolonged wakefulness and sedation; 2) identify the origin of inputs onto the defined LPO neurons; 3) tdetermine the effects of altered connectivity involving active LPO neurons on sleep and sedation status in vivo. The results of the proposed research will provide novel insights into the regulatory mechanisms underlying sedation and the homeostatic drive of sleep. Champ scientifique medical and health sciencesclinical medicineanaesthesiologymedical and health sciencesbasic medicinephysiologyhomeostasis Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Thème(s) MSCA-IF-2016 - Individual Fellowships Appel à propositions H2020-MSCA-IF-2016 Voir d’autres projets de cet appel Régime de financement MSCA-IF-EF-ST - Standard EF Coordinateur IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE Contribution nette de l'UE € 183 454,80 Adresse SOUTH KENSINGTON CAMPUS EXHIBITION ROAD SW7 2AZ LONDON Royaume-Uni Voir sur la carte Région London Inner London — West Westminster Type d’activité Higher or Secondary Education Establishments Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total € 183 454,80
