15 recherche sur le mot-clé 'Prefrontal cortex'

Impaired synaptic function and hyperexcitability of the pyramidal neurons in the prefrontal cortex of autism-associated Shank3 mutant dogs / Feipeng ZHU in Molecular Autism, 15 (2024)  

Public ISBD [article]  inMolecular Autism > 15 (2024) . - 9p. Titre : Impaired synaptic function and hyperexcitability of the pyramidal neurons in the prefrontal cortex of autism-associated Shank3 mutant dogs Type de document : texte imprimé Auteurs : Feipeng ZHU, Auteur ; Qi SHI, Auteur ; Yong-hui JIANG, Auteur ; Yong Q. ZHANG, Auteur ; Hui ZHAO, Auteur Article en page(s) : 9p. Langues : Anglais (eng) Mots-clés : Humans  Dogs  Animals  Autistic Disorder/genetics  Autism Spectrum Disorder  Nerve Tissue Proteins/genetics/metabolism  Pyramidal Cells/metabolism  Synaptic Transmission/genetics  Prefrontal Cortex  Anxiety  Disease Models, Animal  Autism spectrum disorder  Dog  Excitability  Shank3  Synaptic transmission Index. décimale : PER Périodiques Résumé : BACKGROUND: SHANK3 gene is a highly replicated causative gene for autism spectrum disorder and has been well characterized in multiple Shank3 mutant rodent models. When compared to rodents, domestic dogs are excellent animal models in which to study social cognition as they closely interact with humans and exhibit similar social behaviors. Using CRISPR/Cas9 editing, we recently generated a dog model carrying Shank3 mutations, which displayed a spectrum of autism-like behaviors, such as social impairment and heightened anxiety. However, the neural mechanism underlying these abnormal behaviors remains to be identified. METHODS: We used Shank3 mutant dog models to examine possible relationships between Shank3 mutations and neuronal dysfunction. We studied electrophysiological properties and the synaptic transmission of pyramidal neurons from acute brain slices of the prefrontal cortex (PFC). We also examined dendrite elaboration and dendritic spine morphology in the PFC using biocytin staining and Golgi staining. We analyzed the postsynaptic density using electron microscopy. RESULTS: We established a protocol for the electrophysiological recording of canine brain slices and revealed that excitatory synaptic transmission onto PFC layer 2/3 pyramidal neurons in Shank3 heterozygote dogs was impaired, and this was accompanied by reduced dendrite complexity and spine density when compared to wild-type dogs. Postsynaptic density structures were also impaired in Shank3 mutants; however, pyramidal neurons exhibited hyperexcitability. LIMITATIONS: Causal links between impaired PFC pyramidal neuron function and behavioral alterations remain unclear. Further experiments such as manipulating PFC neuronal activity or restoring synaptic transmission in Shank3 mutant dogs are required to assess PFC roles in altered social behaviors. CONCLUSIONS: Our study demonstrated the feasibility of using canine brain slices as a model system to study neuronal circuitry and disease. Shank3 haploinsufficiency causes morphological and functional abnormalities in PFC pyramidal neurons, supporting the notion that Shank3 mutant dogs are new and valid animal models for autism research. En ligne : https://dx.doi.org/10.1186/s13229-024-00587-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538 [article] Impaired synaptic function and hyperexcitability of the pyramidal neurons in the prefrontal cortex of autism-associated Shank3 mutant dogs [texte imprimé] / Feipeng ZHU, Auteur ; Qi SHI, Auteur ; Yong-hui JIANG, Auteur ; Yong Q. ZHANG, Auteur ; Hui ZHAO, Auteur . - 9p. Langues : Anglais (eng) in Molecular Autism > 15 (2024) . - 9p. Mots-clés : Humans  Dogs  Animals  Autistic Disorder/genetics  Autism Spectrum Disorder  Nerve Tissue Proteins/genetics/metabolism  Pyramidal Cells/metabolism  Synaptic Transmission/genetics  Prefrontal Cortex  Anxiety  Disease Models, Animal  Autism spectrum disorder  Dog  Excitability  Shank3  Synaptic transmission Index. décimale : PER Périodiques Résumé : BACKGROUND: SHANK3 gene is a highly replicated causative gene for autism spectrum disorder and has been well characterized in multiple Shank3 mutant rodent models. When compared to rodents, domestic dogs are excellent animal models in which to study social cognition as they closely interact with humans and exhibit similar social behaviors. Using CRISPR/Cas9 editing, we recently generated a dog model carrying Shank3 mutations, which displayed a spectrum of autism-like behaviors, such as social impairment and heightened anxiety. However, the neural mechanism underlying these abnormal behaviors remains to be identified. METHODS: We used Shank3 mutant dog models to examine possible relationships between Shank3 mutations and neuronal dysfunction. We studied electrophysiological properties and the synaptic transmission of pyramidal neurons from acute brain slices of the prefrontal cortex (PFC). We also examined dendrite elaboration and dendritic spine morphology in the PFC using biocytin staining and Golgi staining. We analyzed the postsynaptic density using electron microscopy. RESULTS: We established a protocol for the electrophysiological recording of canine brain slices and revealed that excitatory synaptic transmission onto PFC layer 2/3 pyramidal neurons in Shank3 heterozygote dogs was impaired, and this was accompanied by reduced dendrite complexity and spine density when compared to wild-type dogs. Postsynaptic density structures were also impaired in Shank3 mutants; however, pyramidal neurons exhibited hyperexcitability. LIMITATIONS: Causal links between impaired PFC pyramidal neuron function and behavioral alterations remain unclear. Further experiments such as manipulating PFC neuronal activity or restoring synaptic transmission in Shank3 mutant dogs are required to assess PFC roles in altered social behaviors. CONCLUSIONS: Our study demonstrated the feasibility of using canine brain slices as a model system to study neuronal circuitry and disease. Shank3 haploinsufficiency causes morphological and functional abnormalities in PFC pyramidal neurons, supporting the notion that Shank3 mutant dogs are new and valid animal models for autism research. En ligne : https://dx.doi.org/10.1186/s13229-024-00587-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538

Neuron density is decreased in the prefrontal cortex in Williams syndrome / Caroline HORTON LEW in Autism Research, 10-1 (January 2017)  

Public ISBD [article]  inAutism Research > 10-1 (January 2017) . - p.99-112 Titre : Neuron density is decreased in the prefrontal cortex in Williams syndrome Type de document : texte imprimé Auteurs : Caroline HORTON LEW, Auteur ; Chelsea BROWN, Auteur ; Ursula BELLUGI, Auteur ; Katerina SEMENDEFERI, Auteur Article en page(s) : p.99-112 Langues : Anglais (eng) Mots-clés : frontal pole  design-based stereology  cytoarchitecture  Williams syndrome  prefrontal cortex  neuron density Index. décimale : PER Périodiques Résumé : Williams Syndrome (WS) is a rare neurodevelopmental disorder associated with a hemideletion in chromosome 7, which manifests a distinct behavioral phenotype characterized by a hyperaffiliative social drive, in striking contrast to the social avoidance behaviors that are common in Autism Spectrum Disorder (ASD). MRI studies have observed structural and functional abnormalities in WS cortex, including the prefrontal cortex (PFC), a region implicated in social cognition. This study utilizes the Bellugi Williams Syndrome Brain Collection, a unique resource that comprises the largest WS postmortem brain collection in existence, and is the first to quantitatively examine WS PFC cytoarchitecture. We measured neuron density in layers II/III and V/VI of five cortical areas: PFC areas BA 10 and BA 11, primary motor BA 4, primary somatosensory BA 3, and visual area BA 18 in six matched pairs of WS and typically developing (TD) controls. Neuron density in PFC was lower in WS relative to TD, with layers V/VI demonstrating the largest decrease in density, reaching statistical significance in BA 10. In contrast, BA 3 and BA 18 demonstrated a higher density in WS compared to TD, although this difference was not statistically significant. Neuron density in BA 4 was similar in WS and TD. While other cortical areas were altered in WS, prefrontal areas appeared to be most affected. Neuron density is also altered in the PFC of individuals with ASD. Together these findings suggest that the PFC is targeted in neurodevelopmental disorders associated with sociobehavioral alterations. En ligne : http://dx.doi.org/10.1002/aur.1677 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=303 [article] Neuron density is decreased in the prefrontal cortex in Williams syndrome [texte imprimé] / Caroline HORTON LEW, Auteur ; Chelsea BROWN, Auteur ; Ursula BELLUGI, Auteur ; Katerina SEMENDEFERI, Auteur . - p.99-112. Langues : Anglais (eng) in Autism Research > 10-1 (January 2017) . - p.99-112 Mots-clés : frontal pole  design-based stereology  cytoarchitecture  Williams syndrome  prefrontal cortex  neuron density Index. décimale : PER Périodiques Résumé : Williams Syndrome (WS) is a rare neurodevelopmental disorder associated with a hemideletion in chromosome 7, which manifests a distinct behavioral phenotype characterized by a hyperaffiliative social drive, in striking contrast to the social avoidance behaviors that are common in Autism Spectrum Disorder (ASD). MRI studies have observed structural and functional abnormalities in WS cortex, including the prefrontal cortex (PFC), a region implicated in social cognition. This study utilizes the Bellugi Williams Syndrome Brain Collection, a unique resource that comprises the largest WS postmortem brain collection in existence, and is the first to quantitatively examine WS PFC cytoarchitecture. We measured neuron density in layers II/III and V/VI of five cortical areas: PFC areas BA 10 and BA 11, primary motor BA 4, primary somatosensory BA 3, and visual area BA 18 in six matched pairs of WS and typically developing (TD) controls. Neuron density in PFC was lower in WS relative to TD, with layers V/VI demonstrating the largest decrease in density, reaching statistical significance in BA 10. In contrast, BA 3 and BA 18 demonstrated a higher density in WS compared to TD, although this difference was not statistically significant. Neuron density in BA 4 was similar in WS and TD. While other cortical areas were altered in WS, prefrontal areas appeared to be most affected. Neuron density is also altered in the PFC of individuals with ASD. Together these findings suggest that the PFC is targeted in neurodevelopmental disorders associated with sociobehavioral alterations. En ligne : http://dx.doi.org/10.1002/aur.1677 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=303

NRXN1 depletion in the medial prefrontal cortex induces anxiety-like behaviors and abnormal social phenotypes along with impaired neurite outgrowth in rat / Di WU in Journal of Neurodevelopmental Disorders, 15 (2023)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 15 (2023) Titre : NRXN1 depletion in the medial prefrontal cortex induces anxiety-like behaviors and abnormal social phenotypes along with impaired neurite outgrowth in rat Type de document : texte imprimé Auteurs : Di WU, Auteur ; Jiansheng ZHU, Auteur ; Lianghui YOU, Auteur ; Jingyu WANG, Auteur ; Sufen ZHANG, Auteur ; Zhonghui LIU, Auteur ; Qu XU, Auteur ; Xiaojie YUAN, Auteur ; Lei YANG, Auteur ; Wei WANG, Auteur ; Meiling TONG, Auteur ; Qin HONG, Auteur ; Xia CHI, Auteur Langues : Anglais (eng) Mots-clés : Animals  Rats  Anxiety  Autism Spectrum Disorder/genetics  Calcium-Binding Proteins/genetics  Neural Cell Adhesion Molecules/genetics  Neuronal Outgrowth  Phenotype  Prefrontal Cortex  Proteomics  Anxiety-like behavior  Cell adhesion molecules  Nrxn1  Neurite outgrowth  Neurodevelopmental disorders  Social behavior Index. décimale : PER Périodiques Résumé : BACKGROUND: Neurodevelopmental disorders (NDDs) are a group of disorders induced by abnormal brain developmental processes. The prefrontal cortex (PFC) plays an essential role in executive function, and its role in NDDs has been reported. NDDs are associated with high-risk gene mutations and share partially overlapping genetic abnormalities. METHODS: Neurexins (NRXNs) are related to autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD). NRXN1, an essential susceptibility gene for NDDs, has been reported to be associated with NDDs. However, little is known about its key role in NDDs. RESULTS: NRXN1 downregulation in the medial PFC induced anxiety-like behaviors and abnormal social phenotypes with impaired neurite outgrowth in Sh-NRXN1 in prefrontal neurons. Moreover, tandem mass tag (TMT)-based proteomic analysis of rat brain samples showed that NRXN1 downregulation led to significant proteome alterations, including pathways related to the extracellular matrix, cell membrane, and morphologic change. Furthermore, full-automatic immunoblotting analysis verified the differently expressed proteins related to cell morphology and membrane structure. CONCLUSIONS: Our results confirmed the association of NRXN1 with abnormal behaviors in NDDs and provided richer insights into specific prefrontal knockdown in adolescence, potentially expanding the NRXN1 interactome and contributing to human health. En ligne : https://dx.doi.org/10.1186/s11689-022-09471-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=575 [article] NRXN1 depletion in the medial prefrontal cortex induces anxiety-like behaviors and abnormal social phenotypes along with impaired neurite outgrowth in rat [texte imprimé] / Di WU, Auteur ; Jiansheng ZHU, Auteur ; Lianghui YOU, Auteur ; Jingyu WANG, Auteur ; Sufen ZHANG, Auteur ; Zhonghui LIU, Auteur ; Qu XU, Auteur ; Xiaojie YUAN, Auteur ; Lei YANG, Auteur ; Wei WANG, Auteur ; Meiling TONG, Auteur ; Qin HONG, Auteur ; Xia CHI, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 15 (2023) Mots-clés : Animals  Rats  Anxiety  Autism Spectrum Disorder/genetics  Calcium-Binding Proteins/genetics  Neural Cell Adhesion Molecules/genetics  Neuronal Outgrowth  Phenotype  Prefrontal Cortex  Proteomics  Anxiety-like behavior  Cell adhesion molecules  Nrxn1  Neurite outgrowth  Neurodevelopmental disorders  Social behavior Index. décimale : PER Périodiques Résumé : BACKGROUND: Neurodevelopmental disorders (NDDs) are a group of disorders induced by abnormal brain developmental processes. The prefrontal cortex (PFC) plays an essential role in executive function, and its role in NDDs has been reported. NDDs are associated with high-risk gene mutations and share partially overlapping genetic abnormalities. METHODS: Neurexins (NRXNs) are related to autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD). NRXN1, an essential susceptibility gene for NDDs, has been reported to be associated with NDDs. However, little is known about its key role in NDDs. RESULTS: NRXN1 downregulation in the medial PFC induced anxiety-like behaviors and abnormal social phenotypes with impaired neurite outgrowth in Sh-NRXN1 in prefrontal neurons. Moreover, tandem mass tag (TMT)-based proteomic analysis of rat brain samples showed that NRXN1 downregulation led to significant proteome alterations, including pathways related to the extracellular matrix, cell membrane, and morphologic change. Furthermore, full-automatic immunoblotting analysis verified the differently expressed proteins related to cell morphology and membrane structure. CONCLUSIONS: Our results confirmed the association of NRXN1 with abnormal behaviors in NDDs and provided richer insights into specific prefrontal knockdown in adolescence, potentially expanding the NRXN1 interactome and contributing to human health. En ligne : https://dx.doi.org/10.1186/s11689-022-09471-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=575

Neural correlates of schema-dependent episodic memory and association with behavioral flexibility in autism spectrum disorders and typical development / Kevin M. COOK in Journal of Neurodevelopmental Disorders, 13 (2021)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 13 (2021) Titre : Neural correlates of schema-dependent episodic memory and association with behavioral flexibility in autism spectrum disorders and typical development Type de document : texte imprimé Auteurs : Kevin M. COOK, Auteur ; Xiaozhen YOU, Auteur ; Joseph Bradley CHERRY, Auteur ; Junaid S. MERCHANT, Auteur ; Mary SKAPEK, Auteur ; Meredith D. POWERS, Auteur ; Cara E. PUGLIESE, Auteur ; Lauren KENWORTHY, Auteur ; Chandan J. VAIDYA, Auteur Langues : Anglais (eng) Mots-clés : Adult  Autism Spectrum Disorder  Child  Humans  Memory, Episodic  Mental Recall  Prefrontal Cortex/diagnostic imaging  Recognition, Psychology  Associative memory  Behavioral flexibility  Medial temporal lobe  Executive function  Prefrontal cortex  fMRI  Executive Function. The other authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Conceptual knowledge frameworks termed schemas facilitate memory formation and are posited to support flexible behavior. In adults, the medial temporal lobe (MTL) and medial prefrontal cortex (mPFC) trade-off in supporting schema-based memory formation, such that encoding of subsequently remembered schema-congruent information relies on mPFC, whereas schema-incongruent information relies on MTL. Whether this is true in the immature brain and relates to behavioral flexibility is unknown. In this preliminary investigation, we aimed to replicate the adult findings in typically developing (TD) children and to investigate the relevance to behavioral flexibility by examining a disorder with pathognomonic behavioral rigidity, autism spectrum disorder (ASD). METHODS: Children completed an associative subsequent memory paradigm, encoding object-scene pairs in an MRI scanner and subsequently completing a recognition test outside the scanner after a delay. Recognition performance was back sorted to construct remembered vs forgotten contrasts. One-way ANOVAS were conducted in MTL and mPFC masks for schema-congruency, followed by congruency by flexibility scores. Exploratory analyses were then conducted within the whole brain. RESULTS: As reported in adults, episodic memory was strongest for schema-congruent object-scene pairs, followed by intermediate pairs, and lowest for schema-incongruent pairs in both TD and ASD groups. However, the trade-off between mPFC and MTL in TD children differed from adult reports such that mPFC supported memory for intermediate schema-congruency and left anterior MTL supported memory for schema-congruent pairs. In ASD, mPFC engagement interacted with flexibility such that activation supporting memory for intermediate schema-congruency varied with parent-reported flexibility and was higher in those with more flexible behavior. A similar interaction was also observed in both the left dorsolateral and rostrolateral PFC in whole-brain analysis. CONCLUSION: Our findings provide the first preliminary evidence for the association of schema-based episodic memory formation and behavioral flexibility, an executive function impaired in multiple developmental disorders. Upon replication, this line of research holds promise for memory-based interventions addressing executive problems of behavioral rigidity. En ligne : https://dx.doi.org/10.1186/s11689-021-09388-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574 [article] Neural correlates of schema-dependent episodic memory and association with behavioral flexibility in autism spectrum disorders and typical development [texte imprimé] / Kevin M. COOK, Auteur ; Xiaozhen YOU, Auteur ; Joseph Bradley CHERRY, Auteur ; Junaid S. MERCHANT, Auteur ; Mary SKAPEK, Auteur ; Meredith D. POWERS, Auteur ; Cara E. PUGLIESE, Auteur ; Lauren KENWORTHY, Auteur ; Chandan J. VAIDYA, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 13 (2021) Mots-clés : Adult  Autism Spectrum Disorder  Child  Humans  Memory, Episodic  Mental Recall  Prefrontal Cortex/diagnostic imaging  Recognition, Psychology  Associative memory  Behavioral flexibility  Medial temporal lobe  Executive function  Prefrontal cortex  fMRI  Executive Function. The other authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Conceptual knowledge frameworks termed schemas facilitate memory formation and are posited to support flexible behavior. In adults, the medial temporal lobe (MTL) and medial prefrontal cortex (mPFC) trade-off in supporting schema-based memory formation, such that encoding of subsequently remembered schema-congruent information relies on mPFC, whereas schema-incongruent information relies on MTL. Whether this is true in the immature brain and relates to behavioral flexibility is unknown. In this preliminary investigation, we aimed to replicate the adult findings in typically developing (TD) children and to investigate the relevance to behavioral flexibility by examining a disorder with pathognomonic behavioral rigidity, autism spectrum disorder (ASD). METHODS: Children completed an associative subsequent memory paradigm, encoding object-scene pairs in an MRI scanner and subsequently completing a recognition test outside the scanner after a delay. Recognition performance was back sorted to construct remembered vs forgotten contrasts. One-way ANOVAS were conducted in MTL and mPFC masks for schema-congruency, followed by congruency by flexibility scores. Exploratory analyses were then conducted within the whole brain. RESULTS: As reported in adults, episodic memory was strongest for schema-congruent object-scene pairs, followed by intermediate pairs, and lowest for schema-incongruent pairs in both TD and ASD groups. However, the trade-off between mPFC and MTL in TD children differed from adult reports such that mPFC supported memory for intermediate schema-congruency and left anterior MTL supported memory for schema-congruent pairs. In ASD, mPFC engagement interacted with flexibility such that activation supporting memory for intermediate schema-congruency varied with parent-reported flexibility and was higher in those with more flexible behavior. A similar interaction was also observed in both the left dorsolateral and rostrolateral PFC in whole-brain analysis. CONCLUSION: Our findings provide the first preliminary evidence for the association of schema-based episodic memory formation and behavioral flexibility, an executive function impaired in multiple developmental disorders. Upon replication, this line of research holds promise for memory-based interventions addressing executive problems of behavioral rigidity. En ligne : https://dx.doi.org/10.1186/s11689-021-09388-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574

Imbalance of laminar-specific excitatory and inhibitory circuits of the orbitofrontal cortex in autism / Xuefeng LIU in Molecular Autism, 11 (2020)  

Public ISBD [article]  inMolecular Autism > 11 (2020) . - 83 p. Titre : Imbalance of laminar-specific excitatory and inhibitory circuits of the orbitofrontal cortex in autism Type de document : texte imprimé Auteurs : Xuefeng LIU, Auteur ; Julied BAUTISTA, Auteur ; Edward LIU, Auteur ; Basilis ZIKOPOULOS, Auteur Article en page(s) : 83 p. Langues : Anglais (eng) Mots-clés : Amygdala  Calbindin  Calretinin  Cortical layers  Emotions  Inhibitory neurons  Myelinated axons  Parvalbumin  Prefrontal cortex  Social interactions Index. décimale : PER Périodiques Résumé : BACKGROUND: 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 ligne : http://dx.doi.org/10.1186/s13229-020-00390-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=433 [article] Imbalance of laminar-specific excitatory and inhibitory circuits of the orbitofrontal cortex in autism [texte imprimé] / Xuefeng LIU, Auteur ; Julied BAUTISTA, Auteur ; Edward LIU, Auteur ; Basilis ZIKOPOULOS, Auteur . - 83 p. Langues : Anglais (eng) in Molecular Autism > 11 (2020) . - 83 p. Mots-clés : Amygdala  Calbindin  Calretinin  Cortical layers  Emotions  Inhibitory neurons  Myelinated axons  Parvalbumin  Prefrontal cortex  Social interactions Index. décimale : PER Périodiques Résumé : BACKGROUND: 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 ligne : http://dx.doi.org/10.1186/s13229-020-00390-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=433

Therapeutic Effects of Bilateral Anodal Transcranial Direct Current Stimulation on Prefrontal and Motor Cortical Areas in Children with Autism Spectrum Disorders: A Pilot Study / Hikmat HADOUSH in Autism Research, 13-5 (May 2020)  

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Cellular stress and apoptosis contribute to the pathogenesis of autism spectrum disorder / Daoyin DONG in Autism Research, 11-7 (July 2018)  

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Memory in ASD: have we been barking up the wrong tree? / Jill BOUCHER in Autism, 16-6 (November 2012)  

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Neural Correlates of Set-Shifting in Children With Autism / Benjamin E. YERYS in Autism Research, 8-4 (August 2015)  

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Neurobiological Mechanisms of Anxiety in ASD / John D. HERRINGTON  

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