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The role of 5HT3a inhibitory interneurons in sensory processing

Project description

Mechanistic insight into the processing of sensory information

Sensory stimuli from the environment, such as visual, auditory, or tactile information, are detected by specialised sensory receptors located in our sensory organs and transmitted to the brain. Brain cortical circuits play a crucial role in processing such sensory stimuli and generating our perception of the world around us. Funded by the European Research Council, the SurfaceInhibition project will investigate how different types of inhibitory cells contribute to sensory processing. The focus will be on neural circuits in the cortex that involve inhibitory cells expressing a specific serotonin receptor. By using a combination of techniques, researchers aim to uncover the functions of these inhibitory cells and how they influence sensory perception in health and disease.

Objective

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.

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Topic(s)

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ERC-STG - Starting Grant

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Call for proposal

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(opens in new window) ERC-2014-STG

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Host institution

UNIVERSITETET I OSLO
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 1 350 000,00
Address
PROBLEMVEIEN 5-7
0313 Oslo
Norway

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Region
Norge Oslo og Viken Oslo
Activity type
Higher or Secondary Education Establishments
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Total cost

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€ 1 350 000,00

Beneficiaries (1)

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