Cited by 160Neurotransmitter Receptor Influence on BehaviorNeuroscience and Neuropharmacology ResearchNeural and Behavioral Psychology Studies

Cell-type-specific asynchronous modulation of PKA by dopamine in learning

Open access
Lee, Suk Joon, Lodder, Bart, Chen, Yao, Patriarchi, Tommaso, Tian, Lin, Sabatini, Bernardo L.·2021·Nature

Abstract

Reinforcement learning models postulate that neurons that release dopamine encode information about action and action outcome, and provide a teaching signal to striatal spiny projection neurons in the form of dopamine release 1. Dopamine is thought to guide learning via dynamic and differential modulation of protein kinase A (PKA) in each class of spiny projection neuron 2. However, the real-time relationship between dopamine and PKA in spiny projection neurons remains untested in behaving animals. Here we monitor the activity of dopamine-releasing neurons, extracellular levels of dopamine and net PKA activity in spiny projection neurons in the nucleus accumbens of mice during learning. We find positive and negative modulation of dopamine that evolves across training and is both necessary and sufficient to explain concurrent fluctuations in the PKA activity of spiny projection neurons. Modulations of PKA in spiny projection neurons that express type-1 and type-2 dopamine receptors are dichotomous, such that these neurons are selectively sensitive to increases and decreases, respectively, in dopamine that occur at different phases of learning. Thus, PKA-dependent pathways in each class of spiny projection neuron are asynchronously engaged by positive or negative dopamine signals during learning.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/s41586-020-03050-5

Cites

46 of 46 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • DA release, via cAMP regulation, controls PKA activity in SPNs over tens of seconds, with differential effects on D1 and D2 receptor-expressing neurons.

    “Real-time monitoring of the kinase activity in behaving animals indicates that DA release, via regulation of intracellular cAMP production, controls the activity of protein kinase A (PKA) in SPNs over the timescale of tens of seconds, with differential effects on neurons that express type 1 or type 2 dopamine receptors.122”
  • Dopamine, GABA, and glutamate released by DANs may elicit prolonged waves of postsynaptic effects, from millisecond excitability changes to tens-of-seconds biochemical signaling and excitability.

    “the dopamine, GABA, and glutamate released by DANs may elicit prolonged waves of postsynaptic effects, cascading from the millisecond changes in excitability triggered by ionotropic receptors, to the tens of seconds on biochemical signaling and excitability 109,115,122,123 (Figure 3A).”

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Lee, S. J., Lodder, B., Chen, Y., Patriarchi, T., Tian, L., & Sabatini, B. L.
Affiliations
  • Howard Hughes Medical Institute (US)
  • University of Zurich (CH)
  • University of California, Davis (US)
Corresponding author
Sabatini, Bernardo L.
Venue
Nature
Published
2020-12-23
Volume
590
Issue
7846
Pages
451-456
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
OpenAlex
W3116416936
Cited by
160
References
45
Citations by year
2026: 14 · 2025: 35 · 2024: 25 · 2023: 30 · 2022: 33 · 2021: 18 · 2020: 4 · 2018: 1
FWCI
9.74
Type
journal article
Language
en
Open access
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • Zurich Open Repository and Archive (University of Zurich) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
  • Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
  • Zurich Open Repository and Archive (University of Zurich)
Funders
  • Howard Hughes Medical Institute
  • National Institutes of Health (U01NS013522, R35NS105107)
  • National Institute on Drug Abuse (F32DA035543)
  • National Institute of Neurological Disorders and Stroke (P30NS072030, U01NS090604, R37NS046579, U19NS113201)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
Keywords
dopamine, protein kinase A, medium spiny neurons, nucleus accumbens, reinforcement learning, dopamine receptors, dopamine release, learning, striatum
MeSH terms
Animals, Dopamine, Female, Fluorescence, Learning, Male, Neuronal Plasticity, Nucleus Accumbens, Photometry, Receptors, Dopamine, Cyclic AMP-Dependent Protein Kinases, Mice, Dopaminergic Neurons, GABAergic Neurons

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review