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Hyperconnectivity of Local Neocortical Microcircuitry Induced by Prenatal Exposure to Valproic Acid
Open accessAbstract
Exposure to valproic acid (VPA) during embryogenesis can cause several teratogenic effects, including developmental delays and in particular autism in humans if exposure occurs during the third week of gestation. We examined the postnatal effects of embryonic exposure to VPA on microcircuit properties of juvenile rat neocortex using in vitro electrophysiology. We found that a single prenatal injection of VPA on embryonic day 11.5 causes a significant enhancement of the local recurrent connectivity formed by neocortical pyramidal neurons. The study of the biophysical properties of these connections revealed weaker excitatory synaptic responses. A marked decrease of the intrinsic excitability of pyramidal neurons was also observed. Furthermore, we demonstrate a diminished number of putative synaptic contacts in connection between layer 5 pyramidal neurons. Local hyperconnectivity may render cortical modules more sensitive to stimulation and once activated, more autonomous, isolated, and more difficult to command. This could underlie some of the core symptoms observed in humans prenatally exposed to valproic acid.
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“In the case of apical dendrites, complexity, but not length, is increased on layer II pyramidal neurons in the motor cortex [331], decreased in the medial PFC [297], or is unchanged in layer V pyramidal neurons of the somatosensory cortex following VPA exposure in rodents [301].”
From Autism spectrum disorder: neuropathology and animal models (2017) · cites this paper as [301]
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Metadata
- Authors
- Rinaldi, T., Silberberg, G., & Markram, H.
- Affiliations
- Karolinska Institutet (SE)
- École Polytechnique Fédérale de Lausanne (CH)
- Venue
- Cerebral Cortex
- Publisher
- Oxford University Press (OUP)
- Published
- 2007-07-17
- Volume
- 18
- Issue
- 4
- Pages
- 763-770
- ISSN
- 1047-3211 (ISSN-L)
- 1460-2199
- OpenAlex
- W2148788336
- Cited by
- 184
- References
- 31
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 8 · 2023: 5 · 2022: 13 · 2021: 7 · 2020: 8 · 2019: 7 · 2018: 7 · 2017: 7 · 2016: 16 · 2015: 20 · 2014: 10 · 2013: 17 · 2012: 7
- FWCI
- 3.45
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cerebral Cortex (publishedVersion)
- PubMed (publishedVersion)
- reroDoc Digital Library (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmacological Effects and Toxicity Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- valproic acid, prenatal drug exposure, teratogenicity, autism spectrum disorder, recurrent connectivity, pyramidal neurons, intrinsic excitability, synaptic transmission, layer 5 pyramidal neurons
- MeSH terms
- Animals, Anticonvulsants, Autistic Disorder, Cell Count, Disease Models, Animal, Female, Male, Neural Pathways, Organ Culture Techniques, Pregnancy, Prenatal Exposure Delayed Effects, Valproic Acid, Rats, Wistar, Pyramidal Cells, Patch-Clamp Techniques, Neocortex, Rats
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