The DOI matches its Crossref record; 88 of the 89 references it cites were found in a registry or an index.
Synaptic Activity Unmasks Dopamine D2 Receptor Modulation of a Specific Class of Layer V Pyramidal Neurons in Prefrontal Cortex
Open accessAbstract
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.
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“We found that the D2 receptor is expressed by at least a subset of hiPS cell–derived cortical neurons, similar to what has been reported in vivo49,50”
From Neuronal defects in a human cellular model of 22q11.2 deletion syndrome (2020) · cites this paper as [49]
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“This Gαi coupled receptor has been shown to modulate the function of LTCC48,49.”
From Neuronal defects in a human cellular model of 22q11.2 deletion syndrome (2020) · cites this paper as [49]
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Self-citationEffect of COMT Val 108/158 Met genotype on frontal lobe function and risk for schizophrenia
Egan, M. F., Goldberg, T. E., Kolachana, B. S., Callicott, J. H., Mazzanti, C. M., Straub, R. E., Goldman, D. A., & Weinberger, D. R. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.111134598 · Cited by 2,416
Cortical inhibitory neurons and schizophrenia
Lewis, D. A., Hashimoto, T., & Volk, D. W. (2005) · Nature Reviews Neuroscience · doi:10.1038/nrn1648 · Cited by 2,297
A gene expression atlas of the central nervous system based on bacterial artificial chromosomes
Gong, S., Zheng, C., Doughty, M. L., Losos, K., Didkovsky, N., Schambra, U. B., Nowak, N. J., Joyner, A., Leblanc, G., Hatten, M. E., et al. (2003) · Nature · doi:10.1038/nature02033 · Cited by 2,108
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The Schizophrenia Psychiatric Genome-Wide Association Study (GWAS) Consortium (2011) · Nature Genetics · doi:10.1038/ng.940 · Cited by 1,919
Regulation of parkinsonian motor behaviours by optogenetic control of basal ganglia circuitry
Kravitz, A. V., Freeze, B. S., Parker, P. R. L., Kay, K., Thwin, M. T., Deisseroth, K., & Kreitzer, A. C. (2010) · Nature · doi:10.1038/nature09159 · Cited by 1,885
Self-citationThe principal features and mechanisms of dopamine modulation in the prefrontal cortex
Seamans, J. K., & Yang, C. R. (2004) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2004.05.006 · Cited by 1,592
CaV1.2 Calcium Channel Dysfunction Causes a Multisystem Disorder Including Arrhythmia and Autism
Splawski, I., Timothy, K. W., Sharpe, L. M., Decher, N., Kumar, P., Bloise, R., Napolitano, C., Schwartz, P. J., Joseph, R. M., Condouris, K., et al. (2004) · Cell · doi:10.1016/j.cell.2004.09.011 · Cited by 1,586 · cited 2×
“L-type Ca2+ channels are also implicated in autism (Splawski et al., 2004) and bipolar disorder (Ferreira et al.”
BackgroundCognitive Deficit Caused by Regional Depletion of Dopamine in Prefrontal Cortex of Rhesus Monkey
Brozoski, T. J., Brown, R. M., Rosvold, H. E., & Goldman, P. S. (1979) · Science · doi:10.1126/science.112679 · Cited by 1,500
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Metadata
- 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
- Publisher
- Society for Neuroscience
- Published
- 2012-04-04
- Volume
- 32
- Issue
- 14
- Pages
- 4959-4971
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3352768
- 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
- hybrid
- doi.org
- Licence
- 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
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