Descripción del proyecto
Una visión mecanicista del procesamiento de la información sensorial
Los receptores sensoriales especializados situados en nuestros órganos sensoriales detectan los estímulos sensoriales del entorno, como la información visual, auditiva o táctil, y los transmiten al cerebro. Los circuitos corticales cerebrales desempeñan un papel crucial en el procesamiento de esos estímulos sensoriales y en la generación de nuestra percepción del mundo que nos rodea. En el proyecto SurfaceInhibition, financiado por el Consejo Europeo de Investigación, se estudiará cómo contribuyen los distintos tipos de células inhibidoras al procesamiento sensorial. Se prestará especial atención a los circuitos neuronales del corteza en los que intervienen células inhibidoras que expresan un receptor de serotonina específico. Mediante una combinación de técnicas, los investigadores pretenden descubrir las funciones de estas células inhibidoras y cómo influyen en la percepción sensorial en la salud y la enfermedad.
Objetivo
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.
Ámbito científico
Palabras clave
Programa(s)
Régimen de financiación
ERC-STG - Starting GrantInstitución de acogida
0313 Oslo
Noruega