The DOI matches its Crossref record; 31 of the 31 references it cites were found in a registry or an index.
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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Model of autism: increased ratio of excitation/inhibition in key neural systems
Rubenstein, J. L. R., & Merzenich, M. M. (2003) · Genes, Brain and Behavior · doi:10.1034/j.1601-183x.2003.00037.x · Cited by 2,768
Homeostatic plasticity in the developing nervous system
Turrigiano, G. G., & Nelson, S. B. (2004) · Nature Reviews Neuroscience · doi:10.1038/nrn1327 · Cited by 2,485
Tsodyks, M. V., & Markram, H. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.2.719 · Cited by 1,607
Self-citationJust, M. A. (2004) · Brain · doi:10.1093/brain/awh199 · Cited by 1,589
Castelli, F. (2002) · Brain · doi:10.1093/brain/awf189 · Cited by 1,377
Autism and Abnormal Development of Brain Connectivity: Figure 1.
Belmonte, M. K., Allen, G., Beckel-Mitchener, A., Boulanger, L. M., Carper, R. A., & Webb, S. J. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.3340-04.2004 · Cited by 1,217
Differential signaling via the same axon of neocortical pyramidal neurons
Markram, H., Wang, Y., & Tsodyks, M. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.9.5323 · Cited by 1,102
Self-citationMarkram, H., Lübke, J., Frotscher, M., Roth, A., & Sakmann, B. (1997) · The Journal of Physiology · doi:10.1113/jphysiol.1997.sp022031 · Cited by 960
Self-citationBehavioral Alterations in Rats Prenatally Exposed to Valproic Acid: Animal Model of Autism
Schneider, T., & Przewłocki, R. (2005) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300518 · Cited by 959
Minicolumnar pathology in autism
Casanova, M. F., Buxhoeveden, D. P., Switala, A. E., & Roy, E. (2002) · Neurology · doi:10.1212/wnl.58.3.428 · Cited by 846
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Neurophysiological and Computational Principles of Cortical Rhythms in Cognition
Wang, X.-J. (2010) · Physiological Reviews · doi:10.1152/physrev.00035.2008 · Cited by 1,939
Reconstruction and Simulation of Neocortical Microcircuitry
Markram, H., Muller, E., Ramaswamy, S., Reimann, M. W., Abdellah, M., Sanchez, C. A., Ailamaki, A., Alonso-Nanclares, L., Antille, N., Arsever, S., et al. (2015) · Cell · doi:10.1016/j.cell.2015.09.029 · Cited by 1,557
Self-citationIncreased dendritic spine densities on cortical projection neurons in autism spectrum disorders
Hutsler, J. J., & Zhang, H. (2010) · Brain Research · doi:10.1016/j.brainres.2009.09.120 · Cited by 765
Bourgeron, T. (2009) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2009.06.003 · Cited by 637
Psychosis and autism as diametrical disorders of the social brain
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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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