ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
Synaptic activity unmasks dopamine D2 receptor modulation of a specific class of layer V pyramidal neurons in prefrontal cortex.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 147 papers.
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Who cites it
147 citing papers in PubMed, 222 citations in OpenAlex.
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- Activation by Alcohol of Prefrontal Layer 5 Pyramidal Neurons Depends on Ascending Dopaminergic Input.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Spindle neurons in human cortex possess distinctive firing properties and transcriptomic signatures.Nature communications · 2026Article
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- Behavioral and Prefrontal Circuit Deficits in a Newly DevelopedBiological psychiatry global open science · 2026Article
- Intrinsic Dendritic Integration Features of Prefrontal Layer 5 Pyramidal Cell Subclasses.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Long-Term Memory Engrams From Development to Adulthood.Hippocampus · 2025Review
- Afferent-specific modulation of excitatory synaptic transmission by acetylcholine and serotonin in the prelimbic cortex.bioRxiv : the preprint server for biology · 2025Article
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- Left Ventrolateral Prefrontal Cortical Activity During Reward Expectancy and Mania Risk.JAMA psychiatry · 2025Article
- The Potential Role of Dopamine Pathways in the Pathophysiology of Depression: Current Advances and Future Aspects.CNS & neurological disorders drug targets · 2025Review
- Effect of juvenile social isolation on excitability of prefrontal pyramidal cells with different subcortical axonal projections.Frontiers in cellular neuroscience · 2025Article
- Synaptotagmin-11 deficiency mediates schizophrenia-like behaviors in mice via dopamine over-transmission.Nature communications · 2024Article
- Alpha-synuclein-induced nigrostriatal degeneration and pramipexole treatment disrupt frontostriatal plasticity.NPJ Parkinson's disease · 2024Article
- Encoding of self-initiated actions in axon terminals of the mesocortical pathway.Neurophotonics · 2024Article
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- Cholinergic Activation of Corticofugal Circuits in the Adult Mouse Prefrontal Cortex.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Fear extinction rescuing effects of dopamine and L-DOPA in the ventromedial prefrontal cortex.Translational psychiatry · 2024Article
87 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
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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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.