Cited by 215Neurotransmitter Receptor Influence on BehaviorNeuroscience and Neuropharmacology ResearchSchizophrenia research and treatment

Synaptic Activity Unmasks Dopamine D2 Receptor Modulation of a Specific Class of Layer V Pyramidal Neurons in Prefrontal Cortex

Open access
Gee, Steven, Ellwood, Ian, Patel, Tosha, Luongo, Francisco, Deisseroth, Karl, Sohal, Vikaas S.·2012·The Journal of Neuroscience

Abstract

Dopamine D2 receptors (D2Rs) play a major role in the function of the prefrontal cortex (PFC), and may contribute to prefrontal dysfunction in conditions such as schizophrenia. Here we report that in mouse PFC, D2Rs are selectively expressed by a subtype of layer V pyramidal neurons that have thick apical tufts, prominent h-current, and subcortical projections. Within this subpopulation, the D2R agonist quinpirole elicits a novel afterdepolarization that generates voltage fluctuations and spiking for hundreds of milliseconds. Surprisingly, this afterdepolarization is masked in quiescent brain slices, but is readily unmasked by physiologic levels of synaptic input which activate NMDA receptors, possibly explaining why this phenomenon has not been reported previously. Notably, we could still elicit this afterdepolarization for some time after the cessation of synaptic stimulation. In addition to NMDA receptors, the quinpirole-induced afterdepolarization also depended on L-type Ca 2+channels and was blocked by the selective L-type antagonist nimodipine. To confirm that D2Rs can elicit this afterdepolarization by enhancing Ca 2+(and Ca 2+-dependent) currents, we measured whole-cell Ca 2+potentials that occur after blocking Na+and K+channels, and found quinpirole enhanced these potentials, while the selective D2R antagonist sulpiride had the opposite effect. Thus, D2Rs can elicit a Ca 2+-channel-dependent afterdepolarization that powerfully modulates activity in specific prefrontal neurons. Through this mechanism, D2Rs might enhance outputs to subcortical structures, contribute to reward-related persistent firing, or increase the level of noise in prefrontal circuits.

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 · 10.1523/jneurosci.5835-11.2012

Cites

88 of 88 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?

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

1 of the 89 references couldn’t be matched to a known paper.

Cited by

Sorted by citations

Authors
Gee, S., Ellwood, I., Patel, T., Luongo, F., Deisseroth, K., & Sohal, V. S.
Affiliations
  • University of California, San Francisco (US)
  • Stanford University (US)
Venue
The Journal of Neuroscience
Published
2012-04-04
Volume
32
Issue
14
Pages
4959-4971
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
OpenAlex
W1971825082
Cited by
214
References
89
Citations by year
2026: 6 · 2025: 10 · 2024: 9 · 2023: 16 · 2022: 17 · 2021: 17 · 2020: 15 · 2019: 20 · 2018: 25 · 2017: 17 · 2016: 12 · 2015: 15 · 2014: 15 · 2013: 14 · 2012: 6
FWCI
6.59
Type
journal article
Language
en
Open access
Locations
  • Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Howard Hughes Medical Institute
  • Simons Foundation
  • International Mental Health Research Organization
  • National Alliance for Research on Schizophrenia and Depression
  • National Institute of Mental Health (R00MH085946)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Keywords
dopamine D2 receptor, prefrontal cortex, layer 5 pyramidal neurons, afterdepolarizations, NMDA receptor, L-type calcium channels, nimodipine, quinpirole, sulpiride, synaptic input, hyperpolarization-activated current, subcortical projections, schizophrenia, persistent firing
MeSH terms
Animals, Female, Male, Mice, Inbred C57BL, Neurons, Cell Polarity, Prefrontal Cortex, Receptors, Dopamine D2, Pyramidal Cells, Mice, Synaptic Potentials

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