Post-pubertal Emergence of Prefrontal Cortical Up States Induced by D1-NMDA Co-activation
Abstract
Dopamine-glutamate interactions may contribute to persistent electrical activity in the prefrontal cortex (PFC). We tested whether a D1 modulation of NMDA function can result in persistent depolarization in vitro. D1-NMDA co-activation yielded depolarizing plateaus resembling in vivo up states in PFC pyramidal neurons recorded in slices from adult (PD 45-65), but not pre-pubertal (PD 29-38) rats. These plateaus required intracellular Ca2+, activation of L-type Ca2+ channels and protein kinase A. These events were eliminated by intracellular administration of the voltage-gated Na+ channel blocker QX-314 or by interrupting synaptic activity with bath application of tetrodotoxin or the AMPA antagonist CNQX, suggesting that they require both intrinsic and synaptic mechanisms. These recurrent depolarizations could constitute important elements in cortical information processing, allowing synaptic plasticity and memory functions. Acquiring these PFC D1-NMDA interactions after puberty may be a critical element for developing mature cognitive abilities.
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During embryonic development there is convergence of the various neurotransmitter signaling pathways and they influence each other's development and functioning.
“There is, furthermore, ample evidence now that during embryonic development there is convergence of the various neurotransmitter signaling pathways and influence each other’s development and functioning [153, 227–231].”
From Development of prefrontal cortex (2022) · cites this paper as [228]
Noradrenergic and dopaminergic projections towards forebrain regions, as well as dopaminergic-glutamatergic and dopaminergic-cholinergic interactions, control PFC maturation and functioning.
“The same holds true for noradrenergic and dopaminergic projections towards forebrain regions as well as dopaminergic-glutamatergic and dopaminergic-cholinergic interactions controlling PFC maturation and functioning [227, 228, 231].”
From Development of prefrontal cortex (2022) · cites this paper as [228]
The D1-NMDA interaction in the rodent PFC becomes more robust during adolescence, allowing the emergence of persistent depolarizations in adult brain slices when D1 and NMDA receptors are coactivated.
“The D 1 -NMDA interaction in the rodent PFC becomes more robust during adolescence, allowing the emergence of persistent depolarizations in adult brain slices when D 1 and NMDA receptors are coactivated.11”
From Adolescent Onset of Cortical Disinhibition in Schizophrenia: Insights From Animal Models (2011) · cites this paper as [11]
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- Authors
- Tseng, K. Y.
- Affiliations
- Albany Medical College (US)
- Corresponding author
- Tseng, K. Y.
- Venue
- Cerebral Cortex
- Publisher
- Oxford University Press (OUP)
- Published
- 2004-07-06
- Volume
- 15
- Issue
- 1
- Pages
- 49-57
- ISSN
- 1047-3211 (ISSN-L)
- 1460-2199
- OpenAlex
- W2086932421
- Cited by
- 169
- References
- 57
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 3 · 2022: 4 · 2021: 8 · 2020: 1 · 2019: 3 · 2018: 5 · 2017: 7 · 2016: 9 · 2015: 3 · 2014: 7 · 2013: 16 · 2012: 7
- FWCI
- 4.56
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cerebral Cortex (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (MH57683)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- prefrontal cortex, up states, dopamine D1 receptor, NMDA receptor, dopamine-glutamate interaction, L-type calcium channels, protein kinase A, QX-314, tetrodotoxin, CNQX, synaptic plasticity, puberty, pyramidal neurons, cognitive development
- MeSH terms
- Action Potentials, Animals, Neural Pathways, Organ Culture Techniques, Sexual Maturation, Sodium Channels, Ion Channel Gating, 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine, Receptors, N-Methyl-D-Aspartate, N-Methylaspartate, Prefrontal Cortex, Receptors, Dopamine D1, Cyclic AMP-Dependent Protein Kinases, Pyramidal Cells, Patch-Clamp Techniques, Dopamine Agonists, Excitatory Amino Acid Agonists, Calcium Channels, L-Type, Rats
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