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The Medial Prefrontal Cortex Shapes Dopamine Reward Prediction Errors under State Uncertainty
Open accessAbstract
Animals make predictions based on currently available information. In natural settings, sensory cues may not reveal complete information, requiring the animal to infer the "hidden state" of the environment. The brain structures important in hidden state inference remain unknown. A previous study showed that midbrain dopamine neurons exhibit distinct response patterns depending on whether reward is delivered in 100% (task 1) or 90% of trials (task 2) in a classical conditioning task. Here we found that inactivation of the medial prefrontal cortex (mPFC) affected dopaminergic signaling in task 2, in which the hidden state must be inferred ("will reward come or not?"), but not in task 1, where the state was known with certainty. Computational modeling suggests that the effects of inactivation are best explained by a circuit in which the mPFC conveys inference over hidden states to the dopamine system. VIDEO ABSTRACT.
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“The brain may have dedicated machinery, perhaps in prefrontal cortex [12,13], for computing belief states, which could then be provided to downstream areas, such as the basal ganglia, to perform standard RL algorithms such as TD learning [14].”
From Emergence of belief-like representations through reinforcement learning (2023) · cites this paper as [13]
In the citing paper
“As a working example, we will consider the probabilistic associative learning paradigm where dopamine RPEs were shown to be consistent with a belief representation [7,13].”
From Emergence of belief-like representations through reinforcement learning (2023) · cites this paper as [13]
In the citing paper
“In both tasks, mice were trained to associate an odor cue with probabilistic delivery of a liquid reward 1.2-2.8slater.”
From Emergence of belief-like representations through reinforcement learning (2023) · cites this paper as [13]
In the citing paper
“Previous work has shown that, in animals, prefrontal cortex activity is a necessary component of animals' state representations [13].”
From Emergence of belief-like representations through reinforcement learning (2023) · cites this paper as [13]
In the citing paper
“This work found that inactivating prefrontal cortex in the Starkweather task led to animals' RPEs in Task 2 resembling the RPEs of Task 1.”
From Emergence of belief-like representations through reinforcement learning (2023) · cites this paper as [13]
In the citing paper
“For instance, previous work has suggested that prefrontal cortex may perform state estimation in tasks with hidden states [6,7,12,13].”
From Emergence of belief-like representations through reinforcement learning (2023) · cites this paper as [13]
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Metadata
- Authors
- Starkweather, C. K., Gershman, S. J., & Uchida, N.
- Affiliations
- Harvard University (US)
- Corresponding author
- Gershman, Samuel J.
- Uchida, Naoshige
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2018-05
- Volume
- 98
- Issue
- 3
- Pages
- 616-629.e6
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC5934341
- OpenAlex
- W2797393690
- Cited by
- 136
- References
- 57
- Citations by year
- 2026: 13 · 2025: 23 · 2024: 14 · 2023: 19 · 2022: 12 · 2021: 17 · 2020: 19 · 2019: 13 · 2018: 6
- FWCI
- 6.26
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (R01MH095953, R01MH101207)
- CRCNS (R01-1207833, F30MH112242-01A1, T32MH020017, T32GM007753)
- Harvard Brain Science Initiative
- Simons Collaboration on Global Brain
- Harvard Mind Brain and Behavior
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- medial prefrontal cortex, dopamine, reward prediction error, state uncertainty, hidden state inference, midbrain dopaminergic neurons, neural inactivation, classical conditioning, computational modeling
- MeSH terms
- Action Potentials, Animals, Dopamine, Forecasting, Male, Mice, Inbred C57BL, Mice, Transgenic, Nerve Net, Odorants, Reward, Prefrontal Cortex, Uncertainty, Mice
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