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Neural Representation of Uncertainty in Mouse Visual Cortex

Lead Research Organisation: University of Edinburgh
Department Name: Centre for Discovery Brain Sciences

Abstract

When interacting with our environment, we need to evaluate the potential consequences of our decisions. However, our decisions are usually based on information that is partial and may be ambiguous in different ways. For example, when we are looking for our keys in the flat, we have to take into account that the keys may be partially or fully occluded, we may have imperfect memory about where we put them, or where we found them last time we lost them. Such uncertainty in various modalities (perceptual, motor, cognitive) presents a fundamental challenge that the brain must tackle in order to ensure that behaviour remains adapted to the constraints and demands of the environment. In this interdisciplinary project, we propose to bring together the expertise of neurophysiologists (Rochefort lab) and computational neuroscientists (Lengyel lab) to tackle this critical question in neuroscience: how does the brain encode uncertainty?
A rich body of literature supports the notion that humans and other animals make decisions based on representing and propagating uncertainty (at least approximately) according to the rules of Bayesian decision making, in a broad range of cognitive domains (from sensory perception to motor planning and execution). However, the actual neuronal representations underlying these computations remain unknown. In particular, it is unclear whether uncertainty in the brain is represented opportunistically, i.e. only about decision variables (variables at the final stages of the decision-making process), or whether it is represented ubiquitously, throughout different stages of information processing, including perceptual uncertainty, memory uncertainty, as well as over variables relevant to the decision. In artificial intelligence, there are examples for both strategies, with complementary advantages and disadvantages.
A fundamental factor limiting progress in resolving whether probabilistic representations in the brain are opportunistic or ubiquitous is the lack of experimental paradigms that can distinguish between uncertainty at different stages of decision making (e.g. uncertainty about perceptual vs. decision variables). Thus, the main goal of the project is to analyse behavioural and neural data recorded during a paradigm that has been specifically designed to address this challenge.
We address this question in the context of perceptual decision making, using the mouse primary visual cortex (V1) as a model system. We will use a dataset obtained in the Rochefort lab, in which the activity of large neuronal populations was recorded in V1 while mice were performing a visually-guided goal-directed behavioural task. After training animals on the task, we manipulated the sensory uncertainty of the animals by modifying visual stimulus properties. The project is organised around 2 aims:
- Aim 1. Analyse behavioural data in order to obtain trial-by-trial measures of perceptual and decision uncertainty.
- Aim 2. Determine the neuronal representation of perceptual vs. decision uncertainty in mouse V1.
This project will enable a strong interdisciplinary partnership between a neurophysiology (Rochefort) and a computational neuroscience (Lengyel) lab. This collaboration will drive research to comprehensively understand the encoding of perceptual uncertainty in the adult brain at the cellular, network, and behavioural level. It will also lead to the development of new analysis tools and new computational models of the neuronal implementation of decision-making in the brain. By integrating the skills and expertise from an experimental and a computational lab, members of both labs will develop new interdisciplinary expertise that is of high demand in this field of research.

Technical Summary

Our decisions are usually based on information that is partial and may be ambiguous in several ways. Previous work supports the notion that humans and other animals perform (approximate) Bayesian decision making, appropriately representing and propagating uncertainty, in a broad range of cognitive domains (from perception to motor planning). However, the actual neuronal representations underlying these computations remain unknown. The central question of this project is: at which stage(s) of the decision making process is uncertainty represented in the brain? We address this question in the context of perceptual decision making, using the mouse primary visual cortex (V1) as a model system. We will use a dataset obtained in the Rochefort lab, in which the activity of large neuronal populations was recorded in V1 while mice were performing a visually-guided goal-directed behavioural task. After training animals, we manipulated both their perceptual and decision uncertainty by modifying specific features of the visual stimulus. The project is organised around 2 aims:
- Aim 1. Analyse behavioural data in order to obtain trial-by-trial measures of perceptual and decision uncertainty.
- Aim 2. Determine the neuronal representation of perceptual vs. decision uncertainty in mouse V1.
This project will enable a strong interdisciplinary partnership between a neurophysiology (Rochefort) and a computational neuroscience (Lengyel) lab. This collaboration will drive research to comprehensively understand the encoding of perceptual uncertainty in the adult brain at the cellular, network, and behavioural level. It will also lead to the development of new analysis tools and new computational models of the neuronal implementation of decision-making in the brain. By integrating the skills and expertise from an experimental and a computational lab, members of both labs will develop new interdisciplinary expertise that is of high demand in this field of research.

Publications

10 25 50
 
Description Our results have shed light on the encoding of perceptual uncertainty in the adult mouse brain at the cellular, network, and behavioural level. We have developed new analysis tools and new computational models of the neuronal implementation of decision-making in the brain. By integrating the skills and expertise from an experimental and a computational lab, the post-doctoral researcher employed on this grant as well as a PhD student have developed new interdisciplinary expertise that is of high demand in this field of research.
Exploitation Route Academic use for further research
Sectors Education

 
Title An adaptable, reusable, and light implant for chronic Neuropixels probes 
Description This study presents the design of a new device for using high-density electrophysiological probes ('Neuropixels') chronically and in freely moving rodents. The results demonstrate the system's versatility and ability to record high-quality extracellular data in both mice and rats. This study will be of significant interest to neuroscientists performing chronic electrophysiological recordings. 
Type Of Material Physiological assessment or outcome measure 
Year Produced 2025 
Provided To Others? Yes  
Impact Method used by multiple labs around the world. We specifically adapted the method to allow recordings in female mice (who are smaller than males and thus needed a lighter device). These results will thus increase the potential for more research on female brain functions. 
URL https://elifesciences.org/articles/98522
 
Description Prof. Máté Lengyel 
Organisation University of Cambridge
Department Department of Engineering
Country United Kingdom 
Sector Academic/University 
PI Contribution Scientific discussions and Analysis of data set acquired by Theoklitos Amvrosiadis in my research group.
Collaborator Contribution Analysis of data set, writing of abstract and poster presentation for Cosyne conference 2022 https://www.cosyne.org/poster-session-2 Diverse covariates modulate neural variability: a widespread (sub)cortical phenomenon David Liu, Theoklitos Amvrosiadis, Nathalie Rochefort, Máté Lengyel
Impact Poster, Cosyne conference 2022 https://www.cosyne.org/poster-session-2 Diverse covariates modulate neural variability: a widespread (sub)cortical phenomenon David Liu, Theoklitos Amvrosiadis, Nathalie Rochefort, Máté Lengyel
Start Year 2021
 
Description Cosyne 2023: Panel discussion: Increasing and supporting diversity in your lab 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Discussion about Diversity, equality and Inclusion in neuroscience research laboratories
Panel discussion: Increasing and supporting diversity in your lab
Year(s) Of Engagement Activity 2023
URL https://www.cosyne.org/complete-program
 
Description Invited speaker at an international conference. Presentation of the project 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Invited talk at international conference
Discussion with colleagues from other disciplines. Interdisciplinary collaborations.
Year(s) Of Engagement Activity 2023
URL https://www.fondationdestreilles.com/en/research/seminars/
 
Description Presentation of the results at a conference. Selected abstract for presentation; Cosyne 2024 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Presentation of a poster:
3-011
A new approach for testing specific hypotheses about probabilistic representations
Adam Koblinger, Theoklitos Amvrosiadis, Nathalie L. Rochefort, Mate Lengyel
https://www.cosyne.org/complete-program
Year(s) Of Engagement Activity 2024
URL https://www.cosyne.org/poster-session-3