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dc.contributor.authorLiu, Xuefengen_US
dc.contributor.authorBautista, Julieden_US
dc.contributor.authorLiu, Edwarden_US
dc.contributor.authorZikopoulos, Basilisen_US
dc.coverage.spatialEnglanden_US
dc.date2020-10-06
dc.date.accessioned2021-11-24T19:18:46Z
dc.date.available2021-11-24T19:18:46Z
dc.date.issued2020-10-20
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/33081829
dc.identifier.citationX. Liu, J. Bautista, E. Liu, B. Zikopoulos. 2020. "Imbalance of laminar-specific excitatory and inhibitory circuits of the orbitofrontal cortex in autism.." Mol Autism, Volume 11, Issue 1, 83. https://doi.org/10.1186/s13229-020-00390-x
dc.identifier.issn2040-2392
dc.identifier.urihttps://hdl.handle.net/2144/43411
dc.description.abstractBACKGROUND: The human orbitofrontal cortex (OFC) is involved in assessing the emotional significance of events and stimuli, emotion-based learning, allocation of attentional resources, and social cognition. Little is known about the structure, connectivity and excitatory/inhibitory circuit interactions underlying these diverse functions in human OFC, as well as how the circuit is disrupted in individuals with autism spectrum disorder (ASD). METHODS: We used post-mortem brain tissue from neurotypical adults and individuals with ASD. We examined the morphology and distribution of myelinated axons across cortical layers in OFC, at the single axon level, as a proxy of excitatory pathways. In the same regions, we also examined the laminar distribution of all neurons and neurochemically- and functionally-distinct inhibitory neurons that express the calcium-binding proteins parvalbumin (PV), calbindin (CB), and calretinin (CR). RESULTS: We found that the density of myelinated axons increased consistently towards layer 6, while the average axon diameter did not change significantly across layers in both groups. However, both the density and diameter of myelinated axons were significantly lower in the ASD group compared with the Control group. The distribution pattern and density of the three major types of inhibitory neurons was comparable between groups, but there was a significant reduction in the density of excitatory neurons across OFC layers in ASD. LIMITATIONS: This study is limited by the availability of human post-mortem tissue optimally processed for high-resolution microscopy and immunolabeling, especially from individuals with ASD. CONCLUSIONS: The balance between excitation and inhibition in OFC is at the core of its function, assessing and integrating emotional and social cues with internal states and external inputs. Our preliminary results provide evidence for laminar-specific changes in the ratio of excitation/inhibition in OFC of adults with ASD, with an overall weakening and likely disorganization of excitatory signals and a relative strengthening of local inhibition. These changes likely underlie pathology of major OFC communications with limbic or other cortices and the amygdala in individuals with ASD, and may provide the anatomic basis for disrupted transmission of signals for social interactions and emotions in autism.en_US
dc.description.sponsorshipR01 MH101209 - NIMH NIH HHSen_US
dc.languageeng
dc.language.isoen_US
dc.relation.ispartofMol Autism
dc.rights© The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.en_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.titleImbalance of laminar-specific excitatory and inhibitory circuits of the orbitofrontal cortex in autismen_US
dc.typeArticleen_US
dc.description.versionPublished versionen_US
dc.identifier.doi10.1186/s13229-020-00390-x
pubs.elements-sourcepubmeden_US
pubs.organisational-groupBoston Universityen_US
pubs.organisational-groupBoston University, College of Health & Rehabilitation Sciences: Sargent Collegeen_US
pubs.organisational-groupBoston University, College of Health & Rehabilitation Sciences: Sargent College, Health Sciencesen_US
pubs.publication-statusPublished onlineen_US
dc.identifier.mycv572174


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© The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
Except where otherwise noted, this item's license is described as © The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.