Adolescent Maturation of Cortical Dopamine
Abstract
Dopamine is a critical modulator of prefrontal cortical function, and it is known to be dysfunctional in schizophrenia. Current hypotheses on schizophrenia highlight developmental aspects and genetic predisposition for the disease; yet, symptom onset typically occurs during adolescence. Several aspects of prefrontal cortical circuits and their modulation by dopamine mature postnatally, as late as during adolescence. Here we review studies assessing the postnatal trajectory of dopamine control of GABA interneurons, a neuronal population that has been long suspected to be critical for schizophrenia pathophysiology. Dopamine modulation of fast-spiking interneurons changes dramatically during adolescence (postnatal day 45-50 in rats) with D2 agonists switching from being mildly inhibitory in prepubertal rats to strongly excitatory in young adult rats. In vivo recordings in adult rats reveal that deep-layer pyramidal neurons respond to endogenous DA release with suppression of firing while interneurons are activated. In adult rats with a neonatal ventral hippocampal lesion (NVHL), an extensively studied developmental model of schizophrenia, the maturation in the D2 modulation of interneuron physiology fails to occur, rendering a disinhibited prefrontal cortex. Abnormal interneuron maturation may therefore impair cognitive function in the adult animal.
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The modulation of excitation-inhibition balance in the PFC and hippocampus by DA matures during adolescence.
“It has indeed been proposed that the modulation of excitation-inhibition balance in the PFC and hippocampus by DA matures during adolescence.4”
From Adolescent Onset of Cortical Disinhibition in Schizophrenia: Insights From Animal Models (2011) · cites this paper as [4]
DA is critical for modulating both excitatory glutamate transmission and local inhibition mediated by GABA.
“DA is critical for modulating both excitatory glutamate transmission and local inhibition mediated by GABA. 4”
From Adolescent Onset of Cortical Disinhibition in Schizophrenia: Insights From Animal Models (2011) · cites this paper as [4]
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Adolescent neurostimulation of dopamine circuit reverses genetic deficits in frontal cortex functionPreprint
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- Authors
- O’Donnell, P.
- Affiliations
- University of Maryland, Baltimore (US)
- Corresponding author
- O’Donnell, Patricio
- ORCID
- O’Donnell, Patricio
- Venue
- Neurotoxicity Research
- Published
- 2010-02-12
- Volume
- 18
- Issue
- 3-4
- Pages
- 306-312
- ISSN
- 1029-8428 (ISSN-L)
- 1476-3524
- OpenAlex
- W1964516189
- Cited by
- 107
- References
- 64
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 5 · 2023: 4 · 2022: 7 · 2021: 3 · 2020: 3 · 2019: 4 · 2018: 4 · 2017: 9 · 2016: 8 · 2015: 9 · 2014: 10 · 2013: 21 · 2012: 5
- FWCI
- 1.70
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neurotoxicity Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Mental Health (MH57683)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- dopamine, adolescent brain development, prefrontal cortex, GABAergic interneurons, fast-spiking interneurons, dopamine D2 receptor, schizophrenia, pyramidal neurons, endogenous dopamine release, cognitive function
- MeSH terms
- Action Potentials, Adolescent, Animals, Dopamine, Humans, Nerve Net, Schizophrenia, Schizophrenic Psychology, Prefrontal Cortex
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