Project

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Brain circuit dissection of context-dependent multisensory integration

Applicant El-Boustani Sami
Number 181070
Funding scheme Eccellenza
Research institution Dépt des Neurosciences Fondamentales Faculté de Médecine Université de Genève
Institution of higher education University of Geneva - GE
Main discipline Neurophysiology and Brain Research
Start/End 01.09.2019 - 31.08.2024
Approved amount 1'830'840.00
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Keywords (8)

Synaptic plasticity; Learning; Multisensory; Perceptual inference; Goal-directed behavior; Posterior parietal cortex; Top-down; two-photon imaging

Lay Summary (French)

Lead
Afin de faire face à des environnements complexes, les animaux apprennent à utiliser toutes les informations à leur disposition pour adapter leur comportement. La capacité d'associer des informations provenant de différentes modalités sensorielles est appelée intégration multisensorielle. Ce projet vise à révéler les circuits neuronaux qui orchestrent ce processus lors de la prise de décisions.
Lay summary
L’intégration multisensorielle permet de réagir de manière adaptée au contexte dans lequel on se trouve. Par exemple, recevoir une tape sur l'épaule n'entraînera pas la même réaction dans une allée sombre ou dans une salle de concert bondée. Bien que des études aient montré l’existence de signaux de contexte dans le cerveau, les mécanismes cellulaires sous-jacents restent incompris. Le développement récent d’outils génétiques a fait de la souris un modèle idéal pour répondre à ces questions. Nous étudierons l’existence et l’influence de ces signaux sur la prise de décision chez des souris effectuant des tâches d’association visuo-tactile. Nous postulons l'existence de signaux convergents dans le cortex représentant les entrées sensorielles du monde extérieur et les informations contextuelles internes au cerveau. Les résultats obtenus dans ce projet devraient approfondir considérablement notre compréhension des mécanismes cérébraux sous-jacents à la prise de décision et à l'apprentissage multisensoriel. 


Les résultats de ce projet de recherche fondamentale permettraient de découvrir les mécanismes cellulaires qui façonnent la perception sensorielle et guident le comportement. Ces connaissances sont indispensables pour comprendre les interactions que l’Homme et les animaux entretiennent avec leur environnement et potentiellement les soigner lorsqu’elles sont mal ajustées.
Direct link to Lay Summary Last update: 09.07.2019

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Abstract

Background and rationale: Extracting regularities in the environment to build predictions of forthcoming sensory percepts is an essential cognitive process, which animals use to adjust their behavior and achieve specific goals. Perceptual predictions originate from an internal representation of the world in the brain that is continuously shaped by new experiences and can bias behavior. In humans, visual information is often predictable over time and used as a context to react appropriately to perturbations by other sensory modalities. For instance receiving a tap on the shoulder will not evoke the same reaction if it happens in a dark alley or in a crowded concert venue. Although studies performed on humans and non-human primates have taught us a great deal on the existence of predictive signals and their influence on sensory perception, the underlying cellular mechanism remains elusive. Various circuit models have been suggested to explain how top-down predictive signals could be used to shape bottom-up responses originating from the sensory periphery. These models are difficult to validate in primates where access to genetically defined brain circuits remain limited. Recent developments of genetically-encoded sensors and effectors along with novel behavioral paradigms have positioned mice as an ideal model to address these questions. Here, I propose to study the existence and influence of experience-dependent internal representations on sensory processing and perceptual decision-making in mice performing a context-dependent visuo-tactile multisensory task. Recent studies and preliminary data have identified a cortical area in the mouse brain displaying multisensory responses for visual and tactile sensory inputs. This area is part of a brain region analogous to the primate posterior parietal cortex (PPC) known to be required for cross-modal associations. I will focus on the cellular mechanism underlying multisensory representations in PPC and how these representations differ for bottom-up sensory inputs and top-down experience-dependent prediction signals.Hypothesis: I posit the existence of two converging multisensory representations in the mouse posterior parietal cortex encoding bottom-up external inputs and top-down internal predictions, respectively. I hypothesize that the former originates from primary sensory cortices and impinge on the basal dendrites of pyramidal neurons whereas the latter originates from high-order cortical regions and impinge on the apical dendritic tuft of the same neurons. I further posit that integration of these afferents will generate a decision-related signal that is biased by recent experiences.I propose 3 aims to test this hypothesis: Aim 1: Validate new context-dependent behavioral tasks based on multisensory associations. Aim 2: Characterize multisensory responses in PPC during visuo-tactile stimuli.Aim 3: Identify task-induced synaptic plasticity and top-down modulation of multisensory representations.Methods: Visuo-tactile detection and discrimination tasks with random or grouped trial blocks will be used to study context-dependent behaviors. I will perform optogenetic inactivation experiments to identify multisensory brain regions required to perform the task. I will pinpoint the region in PPC that integrates visual and tactile inputs by using anatomical and unbiased wide-field functional mapping techniques. I will characterize multisensory responses with two-photon calcium imaging at the network and single-cell level using microprisms to image entire cortical columns. I will perform structural and functional dendritic spine imaging in basal and apical dendrites to compare sensory representations and characterize plasticity and top-down modulation induced by the task.Impact for the field: Perceptual decision-making in humans relies on internal predictions that are often altered in neurological disorders involving hallucinations. This work would uncover the cellular and synaptic mechanism that orchestrates how internal representations of the world in the brain shape sensory perception and guide behavior.
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