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

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

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

DOI 10.1523/jneurosci.5835-11.2012PMC PMC3352768

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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.

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Corticostriatal connectivity and its role in disease
Shepherd, G. M. G. (2013) · Nature Reviews Neuroscience · doi:10.1038/nrn3469 · Cited by 824
Dopaminergic modulation of synaptic transmission in cortex and striatum
Tritsch, N. X., & Sabatini, B. L. (2012) · Neuron · doi:10.1016/j.neuron.2012.09.023 · Cited by 756
Dissecting the diversity of midbrain dopamine neurons
Roeper, J. (2013) · Trends in Neurosciences · doi:10.1016/j.tins.2013.03.003 · Cited by 395
Prefrontal cortex circuits in depression and anxiety: contribution of discrete neuronal populations and target regions
Hare, B. D., & Duman, R. S. (2020) · Molecular Psychiatry · doi:10.1038/s41380-020-0685-9 · Cited by 366
Prefrontal dopamine and behavioral flexibility: shifting from an “inverted-U” toward a family of functions
Floresco, S. B. (2013) · Frontiers in Neuroscience · doi:10.3389/fnins.2013.00062 · Cited by 336

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Authors: Gee, S., Ellwood, I., Patel, T., Luongo, F., Deisseroth, K., & Sohal, V. S.
Affiliations: University of California, San Francisco (US)
Stanford University (US)
ORCID: Luongo, Francisco
Deisseroth, Karl
Sohal, Vikaas S.
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
DOI: 10.1523/jneurosci.5835-11.2012
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: cc-by-nc-sa
creativecommons.org/licenses/by-nc-sa/4.0/ (vor, 183 d)
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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Synaptic Activity Unmasks Dopamine D2 Receptor Modulation of a Specific Class of Layer V Pyramidal Neurons in Prefrontal Cortex

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