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Serotonin neurons modulate learning rate through uncertainty.

ABSTRACT: Regulating how fast to learn is critical for flexible behavior. Learning about the consequences of actions should be slow in stable environments, but accelerate when that environment changes. Recognizing stability and detecting change are difficult in environments with noisy relationships between actions and outcomes. Under these conditions, theories propose that uncertainty can be used to modulate learning rates ("meta-learning"). We show that mice behaving in a dynamic foraging task exhibit choice behavior that varied as a function of two forms of uncertainty estimated from a meta-learning model. The activity of dorsal raphe serotonin neurons tracked both types of uncertainty in the foraging task as well as in a dynamic Pavlovian task. Reversible inhibition of serotonin neurons in the foraging task reproduced changes in learning predicted by a simulated lesion of meta-learning in the model. We thus provide a quantitative link between serotonin neuron activity, learning, and decision making.

SUBMITTER: Grossman CD

PROVIDER: S-EPMC8825708 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Serotonin neurons modulate learning rate through uncertainty.

Grossman Cooper D CD Bari Bilal A BA Cohen Jeremiah Y JY

Current biology : CB 20211221 3

Regulating how fast to learn is critical for flexible behavior. Learning about the consequences of actions should be slow in stable environments, but accelerate when that environment changes. Recognizing stability and detecting change are difficult in environments with noisy relationships between actions and outcomes. Under these conditions, theories propose that uncertainty can be used to modulate learning rates ("meta-learning"). We show that mice behaving in a dynamic foraging task exhibit ch ...[more]

PMID: 34936883

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Project description:[Correction Notice: An Erratum for this article was reported online in Journal of Experimental Psychology: General on Jan 14 2021 (see record 2021-07705-001). In the article, formatting for UK Research Councils funding was omitted. The author note and copyright line now reflect the standard acknowledgment of and formatting for the funding received for this article. All versions of this article have been corrected.] Attention determines which cues receive processing and are learned about. Learning, however, leads to attentional biases. In the study of animal learning, in some circumstances, cues that have been previously predictive of their consequences are subsequently learned about more than are nonpredictive cues, suggesting that they receive more attention. In other circumstances, cues that have previously led to uncertain consequences are learned about more than are predictive cues. In human learning, there is a clear role for predictiveness, but a role for uncertainty has been less clear. Here, in a human learning task, we show that cues that led to uncertain outcomes were subsequently learned about more than were cues that were previously predictive of their outcomes. This effect occurred when there were few uncertain cues. When the number of uncertain cues was increased, attention switched to predictive cues. This pattern of results was found for cues (1) that were uncertain because they led to 2 different outcomes equally often in a nonpredictable manner and (2) that were used in a nonlinear discrimination and were not predictive individually but were predictive in combination with other cues. This suggests that both the opposing predictiveness and uncertainty effects were determined by the relationship between individual cues and outcomes rather than the predictive strength of combined cues. These results demonstrate that learning affects attention; however, the precise nature of the effect on attention depends on the level of task complexity, which reflects a potential switch between exploration and exploitation of cues. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Project description:Serotonin is a neurotransmitter involved in many psychiatric diseases. In humans, a lack of 5-HT2B receptors is associated with serotonin-dependent phenotypes, including impulsivity and suicidality. A lack of 5-HT2B receptors in mice eliminates the effects of molecules that directly target serotonergic neurons including amphetamine derivative serotonin releasers, and selective serotonin reuptake inhibitor antidepressants. In this work, we tested the hypothesis that 5-HT2B receptors directly and positively regulate raphe serotonin neuron activity. By ex vivo electrophysiological recordings, we report that stimulation by the 5-HT2B receptor agonist, BW723C86, increased the firing frequency of serotonin Pet1-positive neurons. Viral overexpression of 5-HT2B receptors in these neurons increased their excitability. Furthermore, in vivo 5-HT2B-receptor stimulation by BW723C86 counteracted 5-HT1A autoreceptor-dependent reduction in firing rate and hypothermic response in wild-type mice. By a conditional genetic ablation that eliminates 5-HT2B receptor expression specifically and exclusively from Pet1-positive serotonin neurons (Htr2b 5-HTKO mice), we demonstrated that behavioral and sensitizing effects of MDMA (3,4-methylenedioxy-methamphetamine), as well as acute behavioral and chronic neurogenic effects of the antidepressant fluoxetine, require 5-HT2B receptor expression in serotonergic neurons. In Htr2b 5-HTKO mice, dorsal raphe serotonin neurons displayed a lower firing frequency compared to control Htr2b lox/lox mice as assessed by in vivo extracellular recordings and a stronger hypothermic effect of 5-HT1A-autoreceptor stimulation was observed. The increase in head-twitch response to DOI (2,5-dimethoxy-4-iodoamphetamine) further confirmed the lower serotonergic tone resulting from the absence of 5-HT2B receptors in serotonin neurons. Together, these observations indicate that the 5-HT2B receptor acts as a direct positive modulator of serotonin Pet1-positive neurons in an opposite way as the known 5-HT1A-negative autoreceptor.

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Serotonin neurons modulate learning rate through uncertainty.

Publications

Serotonin neurons modulate learning rate through uncertainty.

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