Abstract

The gradual accumulation of sensory evidence is a crucial component of perceptual decision making, but its neural mechanisms are still poorly understood. Given the wide availability of genetic and optical tools for mice, they can be useful model organisms for the study of these phenomena; however, behavioral tools are largely lacking. Here, we describe a new evidence-accumulation task for head-fixed mice navigating in a virtual reality (VR) environment. As they navigate down the stem of a virtual T-maze, they see brief pulses of visual evidence on either side, and retrieve a reward on the arm with the highest number of pulses. The pulses occur randomly with Poisson statistics, yielding a diverse yet well-controlled stimulus set, making the data conducive to a variety of computational approaches. A large number of mice of different genotypes were able to learn and consistently perform the task, at levels similar to rats in analogous tasks. They are sensitive to side differences of a single pulse, and their memory of the cues is stable over time. Moreover, using non-parametric as well as modeling approaches, we show that the mice indeed accumulate evidence: they use multiple pulses of evidence from throughout the cue region of the maze to make their decision, albeit with a small overweighting of earlier cues, and their performance is affected by the magnitude but not the duration of evidence. Additionally, analysis of the mice's running patterns revealed that trajectories are fairly stereotyped yet modulated by the amount of sensory evidence, suggesting that the navigational component of this task may provide a continuous readout correlated to the underlying cognitive variables. Our task, which can be readily integrated with state-of-the-art techniques, is thus a valuable tool to study the circuit mechanisms and dynamics underlying perceptual decision making, particularly under more complex behavioral contexts.

Highlights

  • Making decisions based on noisy or ambiguous sensory evidence is a task animals must face on a daily basis

  • We have developed a novel pulse-based evidence accumulation task for mice navigating in virtual reality (VR) (Figure 1, Supplementary Movie 1)

  • We have developed a new virtual navigation-based, pulsed evidence-accumulation task for head-fixed mice, along with tools to quantify their performance and behavioral strategy

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Summary

Introduction

Making decisions based on noisy or ambiguous sensory evidence is a task animals must face on a daily basis. Amidst tall grass, deciding a route to a partially occluded food source (say, a corn plant) might require gradual accumulation of visual evidence, i.e., short glimpses of what may or may not be part of that plant. This example highlights another important point about decision-making, namely that it is often performed in conjunction with other complex behaviors and can itself be a dynamic process occurring over seconds-long timescales. How the brain gradually accumulates sensory evidence has been the topic of extensive studies performed primarily in primates (Gold and Shadlen, 2007). Rodents provide many complementary advantages to the use of primates, such as lower cost, larger scalability, and, for mice, the wide availability of an ever-expanding arsenal of tools to record from and manipulate circuits with great spatiotemporal and genetic specificity in behaving animals (Svoboda and Yasuda, 2006; Dombeck et al, 2007; Luo et al, 2008; Deisseroth, 2011; Chen et al, 2013; Guo et al, 2014; Rickgauer et al, 2014; Sofroniew et al, 2016; Song et al, 2017)

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