Activity patterns of serotonin neurons underlying cognitive flexibility.

Sara Matias,Eran Lottem,Zachary F Mainen,Guillaume P Dugué

doi:10.7554/elife.20552

Sara Matias, Eran Lottem + Show 2 more

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https://doi.org/10.7554/elife.20552

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Abstract

Serotonin is implicated in mood and affective disorders. However, growing evidence suggests that a core endogenous role is to promote flexible adaptation to changes in the causal structure of the environment, through behavioral inhibition and enhanced plasticity. We used long-term photometric recordings in mice to study a population of dorsal raphe serotonin neurons, whose activity we could link to normal reversal learning using pharmacogenetics. We found that these neurons are activated by both positive and negative prediction errors, and thus report signals similar to those proposed to promote learning in conditions of uncertainty. Furthermore, by comparing the cue responses of serotonin and dopamine neurons, we found differences in learning rates that could explain the importance of serotonin in inhibiting perseverative responding. Our findings show how the activity patterns of serotonin neurons support a role in cognitive flexibility, and suggest a revised model of dopamine-serotonin opponency with potential clinical implications.

Highlights

The findings suggest that together with dopamine, another molecule involved in learning from rewards, serotonin could play an important role during reversal learning
We first sought causal evidence that 5-HT neurons were linked to reversal learning in mice engaged in such a task by using a pharmacogenetic approach to silence 5-HT neurons (Ray et al, 2011; Teissier et al, 2015; Armbruster et al, 2007)
After a fixed 2 s trace period, each odor was followed by a tone and a specific outcome, or unconditioned stimulus (US) (Figure 1B top)

Summary

Introduction

Serotonin (5-HT) is classically known to be implicated in mood and affective disorders (Dayan and Huys, 2009; Cools et al, 2011; Li et al, 2012), but it plays a fundamental role when organisms need to adapt to sudden changes in the causal structure of an environment, such as during extinction and reversal learning paradigms (Clarke et al, 2004, 2007; Boulougouris and Robbins, 2010; Bari et al, 2010; Brigman et al, 2010; Berg et al, 2014) These studies have shown that 5-HT depletion, in the orbitofrontal cortex (OFC) of primates, causes perseverative errors, that is, difficulties in stopping responses to previously rewarded stimuli which are no longer reinforced, without affecting learning of new associations or retention of learned associations (Clarke et al, 2007).

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