Chronic Gestational Exposure to Ethanol Leads to Enduring Aberrances in Cortical Form and Function in the Medial Prefrontal Cortex
Open accessAbstract
BACKGROUND: Exposure to ethanol (EtOH) in utero alters the disposition of tangentially migrating GABAergic interneurons in the fetal brain. The medial ganglionic eminence (MGE) gives rise to a large portion of cortical GABAergic interneurons, including the parvalbumin-expressing interneurons that shape and contribute to inhibitory/excitatory (I/E) balance of the intracortical circuit. Here, we investigated in the mouse medial prefrontal cortex (mPFC) the hypothesis that low levels of maternal EtOH consumption from closure of the neural tube embryonic day (E) 9.5 until birth result in an enduring interneuronopathy. METHODS: Pregnant mice were subjected to a 2% w/w EtOH consumption regimen starting at neural tube closure and ending at parturition. Neurogenesis in the MGE was assessed by 5-bromo-2-deoxyuridine (BrdU) immunofluorescence at E12.5. The count and distribution of parvalbumin-expressing interneurons were determined in adult animals, and patch clamp electrophysiology was performed to determine GABAergic function and I/E balance. Open-field behavior in adult mice was assessed to determine whether the EtOH-exposed cohort displayed a lasting alteration in exploratory behavior. RESULTS: In embryos exposed to EtOH in utero, we found increased BrdU labeling in the MGE, pointing to increased neurogenesis. Adult mice prenatally exposed to EtOH were hyperactive, and this was associated with an increase in parvalbumin-expressing GABAergic interneurons in the mPFC. In addition, prenatal EtOH exposure altered the balance between spontaneous inhibitory and excitatory synaptic input and attenuated GABAergic tone in layer V mPFC pyramidal neurons in juvenile mice. CONCLUSIONS: These findings underscore that altered migration of GABAergic interneurons contributes to the EtOH-induced aberration of cortical development and that these effects persist into adulthood as altered cortical form and function.
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Structurally, the prefrontal cortical thickness is affected after prenatal alcohol exposure and it matures with a smaller number of excitatory neurons and more GABAergic ones, disrupting the excitatory/inhibitory balance severely.
“Structurally, the prefrontal cortical thickness is affected after prenatal alcohol exposure and it matures with a smaller number of excitatory neurons and more GABAergic ones disrupting the excitatory/inhibitory balance severely [319–321].”
From Development of prefrontal cortex (2022) · cites this paper as [321]
The Results report more parvalbumin-expressing GABAergic interneurons in the adult mouse mPFC, and the Results and Discussion report an altered inhibitory/excitatory synaptic ratio after prenatal ethanol exposure (page numbers unavailable). They report reduced excitatory synaptic-event frequency, not a smaller number of excitatory neurons. The passages found do not establish a change in cortical thickness, and the Discussion says the net effect of the synaptic change and reduced tonic inhibition remains unclear. (LLM, conf=0.87)
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- Authors
- Skorput, A. G. J., & Yeh, H. H.
- Affiliations
- University of Minnesota (US)
- Dartmouth–Hitchcock Medical Center (US)
- Corresponding author
- Yeh, Hermes H.
- ORCID
- Yeh, Hermes H.
- Venue
- Alcoholism: Clinical and Experimental Research
- Publisher
- Wiley
- Published
- 2016-05-31
- Volume
- 40
- Issue
- 7
- Pages
- 1479-1488
- ISSN
- 0145-6008 (ISSN-L)
- PMC
- PMC5559699
- OpenAlex
- W2415149133
- Cited by
- 50
- References
- 48
- Citations by year
- 2026: 8 · 2025: 1 · 2024: 1 · 2023: 3 · 2022: 5 · 2021: 12 · 2020: 6 · 2019: 4 · 2018: 1 · 2017: 7 · 2016: 2
- FWCI
- 5.43
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Alcoholism Clinical and Experimental Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Presbyterian Historical Society (R01 AA023410, R21 AA024036)
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Substance Exposure Effects
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- prenatal alcohol exposure, fetal alcohol spectrum disorders, medial prefrontal cortex, medial ganglionic eminence, GABAergic interneurons, parvalbumin interneurons, interneuron migration, cortical neurogenesis, excitation-inhibition balance, GABAergic tone, pyramidal neurons, hyperactivity, exploratory behavior, cortical development
- MeSH terms
- Alcohol Drinking, Ethanol, Animals, Cell Movement, Exploratory Behavior, Female, Interneurons, Male, Mice, Transgenic, Pregnancy, Prenatal Exposure Delayed Effects, Prefrontal Cortex, Mice, Neurogenesis, GABAergic Neurons
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