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Presynaptic regulation of recurrent excitation by D1 receptors in prefrontal circuits
Open accessAbstract
The prefrontal cortex plays a fundamental role in the working memory functions of the cerebral cortex and is also the site of dysfunction in several neurological and psychiatric disorders, including schizophrenia. Prefrontal neurons are distinguished by their capacity for sustained activity during the time a stimulus is held in memory, and this mnemonic response is considered a substrate for a variety of cognitive functions. The neuronal basis for sustained activity in prefrontal neurons is unknown but is thought to involve recurrent excitation among pyramidal neurons. Recent studies in awake behaving monkeys have demonstrated that the persistent activity in prefrontal neurons is modulated by dopamine. To examine the mechanisms by which dopamine might modulate transmission in local excitatory circuits, we have performed dual whole-cell recordings in connected pyramidal cell pairs with and without dopamine application. We find that dopamine reduces the efficacy of unitary excitatory neurotransmission in layer V pyramidal cells by decreasing its reliability. These effects, which are reproduced by a selective D1 agonist and blocked by a D1 antagonist, are independent of voltage changes and are not attenuated by blockade of sodium and potassium channels in the postsynaptic neurons. We conclude that attenuation of local horizontal excitatory synaptic transmission in layer V pyramidal neurons by dopamine is through D1 actions at a presynaptic site.
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“Dopamine also reduces recurrent excitation in layer V pyramidal neurons 50”
From Mechanisms of synaptic transmission dysregulation in the prefrontal cortex: pathophysiological implications (2022) · cites this paper as [50]
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Metadata
- Authors
- Gao, W.-J., Krimer, L. S., & Goldman-Rakic, P. S.
- Affiliations
- Yale University (US)
- Section of Neurobiology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510
- ORCID
- Gao, Wen-Jun
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2000-12-26
- Volume
- 98
- Issue
- 1
- Pages
- 295-300
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC14584
- OpenAlex
- W2154397718
- Cited by
- 257
- References
- 37
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 8 · 2023: 2 · 2022: 2 · 2021: 4 · 2020: 9 · 2019: 6 · 2018: 6 · 2017: 5 · 2016: 4 · 2015: 11 · 2014: 10 · 2013: 15 · 2012: 7
- FWCI
- 5.29
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (R01MH038546, P50 MH44866, R01 MH38546, R37MH038546, P50MH044866, R01MH085666)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Keywords
- dopamine D1 receptor, presynaptic modulation, recurrent excitation, prefrontal cortex, layer 5 pyramidal neurons, persistent neuronal activity, working memory, synaptic reliability, schizophrenia
- MeSH terms
- Animals, Benzazepines, Dopamine, Ferrets, Synaptic Transmission, Schizophrenia, Wakefulness, Potassium Channels, Sodium Channels, Prefrontal Cortex, Receptors, Dopamine D1, Presynaptic Terminals, Pyramidal Cells, Patch-Clamp Techniques, Dopamine Agonists, Dopamine Antagonists, Excitatory Postsynaptic Potentials, Raclopride, In Vitro Techniques
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