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The role of 5HT3a inhibitory interneurons in sensory processing

Description du projet

Aperçu mécaniste du traitement de l’information sensorielle

Les stimuli sensoriels provenant de l’environnement, tels que les informations visuelles, auditives ou tactiles, sont détectés par des récepteurs sensoriels spécialisés situés dans nos organes sensoriels et transmis au cerveau. Les circuits corticaux du cerveau jouent un rôle crucial dans le traitement de ces stimuli sensoriels et dans la perception du monde qui nous entoure. Financé par le Conseil européen de la recherche, le projet SurfaceInhibition étudiera la manière dont différents types de cellules inhibitrices contribuent au traitement sensoriel. L’accent sera mis sur les circuits neuronaux du cortex qui impliquent des cellules inhibitrices exprimant un récepteur spécifique de la sérotonine. Les chercheurs visent à découvrir, à l’aide d’une combinaison de techniques, les fonctions de ces cellules inhibitrices et la manière dont elles influencent la perception sensorielle dans la santé et la maladie.

Objectif

How do cortical circuits process sensory stimuli that leads to perception? Sensory input is encoded by complex interactions between principal excitatory neurons and a diverse population of inhibitory cells. Distinct inhibitory neurons control different subcellular domains of target principal neurons, suggesting specific roles of different cells during sensory processing. However, the individual contribution of these inhibitory subtypes to sensory processing remains poorly understood. This is mainly due to the technical challenges of recording the activity of identified cell types in-vivo, in response to quantified sensory stimuli. Therefore, I propose a novel approach based on four pillars: 1) An optically accessible circuit in the superficial layers of the cortex, comprised of inhibitory cells expressing the serotonin receptor 5HT3a, and the distal dendrites of pyramidal neurons. 2) A novel combination of electrophysiology and 3D two-photon imaging to simultaneously record the activity of morphologically identified 5HT3a cells and their dendritic targets. 3) A head-fixed perceptual decision task, whereby mice use their whiskers to determine the location of an object, allowing an accurate description of the sensory stimulus. 4) The integration of experimental data and computer models to gain mechanistic insights into circuit functions. The 5HT3a cells and the distal dendrites of pyramidal neurons receive ‘top-down’ contextual information from other cortical areas that is essential for constructing meaningful perceptions of sensory stimuli. Thus I hypothesize that 5HT3a cells influence sensory perceptions by controlling the excitability of the pyramidal cell distal dendrites that integrate top-down and sensory input. Thus, I will not only reveal novel functions of inhibitory neurons, I will also shed light on how top-down and sensory input is integrated, and I will provide novel methods to test the functions of other cell types in normal mice and disease models.

Régime de financement

ERC-STG - Starting Grant

Institution d’accueil

UNIVERSITETET I OSLO
Contribution nette de l'UE
€ 1 350 000,00
Adresse
PROBLEMVEIEN 5-7
0313 Oslo
Norvège

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Région
Norge Oslo og Viken Oslo
Type d’activité
Higher or Secondary Education Establishments
Liens
Coût total
€ 1 350 000,00

Bénéficiaires (1)