2 recherche sur le mot-clé 'Inhibitory'

Enhanced Social Dominance and Altered Neuronal Excitability in the Prefrontal Cortex of Male KCC2b Mutant Mice / A. M. J. ANACKER in Autism Research, 12-5 (May 2019)  

Public ISBD [article]  inAutism Research > 12-5 (May 2019) . - p.732-743 Titre : Enhanced Social Dominance and Altered Neuronal Excitability in the Prefrontal Cortex of Male KCC2b Mutant Mice Type de document : Texte imprimé et/ou numérique Auteurs : A. M. J. ANACKER, Auteur ; J. T. MORAN, Auteur ; S. SANTARELLI, Auteur ; C. G. FORSBERG, Auteur ; T. D. ROGERS, Auteur ; G. D. STANWOOD, Auteur ; B. J. HALL, Auteur ; E. DELPIRE, Auteur ; J. VEENSTRA-VANDERWEELE, Auteur ; M. D. SAXE, Auteur Article en page(s) : p.732-743 Langues : Anglais (eng) Mots-clés : Gaba  autism  dominance  excitatory  inhibitory  social Index. décimale : PER Périodiques Résumé : The K-Cl cotransporter KCC2 is essential in the development of the "GABA switch" that produces a change in neuronal responses to GABA signaling from excitatory to inhibitory early in brain development, and alterations in this progression have previously been hypothesized to play a causal role in autism spectrum disorder (ASD). We investigated the KCC2b (Slc12a5) heterozygous knockout mouse using a battery of rodent behavioral tests relevant to core and comorbid ASD symptoms. Compared to wild-type littermates, KCC2(+/-) mice were normal in standard measures of locomotor activity, grooming and digging behaviors, and social, vocalization, and anxiety-like behaviors. However, KCC2(+/-) mice exhibited increased social dominance behaviors and increased amplitude of spontaneous postsynaptic currents in the medial prefrontal cortex (PFC) that were previously implicated in governing social hierarchy and dominance behaviors. Treatment of wild-type mouse brain slices with the KCC2 inhibitor VU0240511 increased the amplitude and frequency of excitatory postsynaptic currents, partially recapitulating the phenotype of KCC2(+/-) mice. These findings indicate that the activity of KCC2 plays a role in social dominance, in parallel with effects on PFC signaling, further suggesting that KCC2 function has some relevance to social behavior but without the breadth of impact on autism-like behavior suggested by previous studies. Further testing could assess whether KCC2 alters other circuits and whether additional factors such as environmental insults may precipitate autism-related behavioral phenotypes. Autism Research 2019, 12: 732-743. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: A mouse model of altered chloride transporter expression was used to look for a role in behaviors and brain function relevant to autism. There was an imbalance in signaling in the prefrontal cortex, and increased social dominance behavior, although other autism-related behaviors were not changed. These findings indicate that altered chloride transporter function affects prefrontal cortex function and social dominance without a broader impact on autism-like behaviors. En ligne : http://dx.doi.org/10.1002/aur.2098 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=397 [article] Enhanced Social Dominance and Altered Neuronal Excitability in the Prefrontal Cortex of Male KCC2b Mutant Mice [Texte imprimé et/ou numérique] / A. M. J. ANACKER, Auteur ; J. T. MORAN, Auteur ; S. SANTARELLI, Auteur ; C. G. FORSBERG, Auteur ; T. D. ROGERS, Auteur ; G. D. STANWOOD, Auteur ; B. J. HALL, Auteur ; E. DELPIRE, Auteur ; J. VEENSTRA-VANDERWEELE, Auteur ; M. D. SAXE, Auteur . - p.732-743. Langues : Anglais (eng) in Autism Research > 12-5 (May 2019) . - p.732-743 Mots-clés : Gaba  autism  dominance  excitatory  inhibitory  social Index. décimale : PER Périodiques Résumé : The K-Cl cotransporter KCC2 is essential in the development of the "GABA switch" that produces a change in neuronal responses to GABA signaling from excitatory to inhibitory early in brain development, and alterations in this progression have previously been hypothesized to play a causal role in autism spectrum disorder (ASD). We investigated the KCC2b (Slc12a5) heterozygous knockout mouse using a battery of rodent behavioral tests relevant to core and comorbid ASD symptoms. Compared to wild-type littermates, KCC2(+/-) mice were normal in standard measures of locomotor activity, grooming and digging behaviors, and social, vocalization, and anxiety-like behaviors. However, KCC2(+/-) mice exhibited increased social dominance behaviors and increased amplitude of spontaneous postsynaptic currents in the medial prefrontal cortex (PFC) that were previously implicated in governing social hierarchy and dominance behaviors. Treatment of wild-type mouse brain slices with the KCC2 inhibitor VU0240511 increased the amplitude and frequency of excitatory postsynaptic currents, partially recapitulating the phenotype of KCC2(+/-) mice. These findings indicate that the activity of KCC2 plays a role in social dominance, in parallel with effects on PFC signaling, further suggesting that KCC2 function has some relevance to social behavior but without the breadth of impact on autism-like behavior suggested by previous studies. Further testing could assess whether KCC2 alters other circuits and whether additional factors such as environmental insults may precipitate autism-related behavioral phenotypes. Autism Research 2019, 12: 732-743. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: A mouse model of altered chloride transporter expression was used to look for a role in behaviors and brain function relevant to autism. There was an imbalance in signaling in the prefrontal cortex, and increased social dominance behavior, although other autism-related behaviors were not changed. These findings indicate that altered chloride transporter function affects prefrontal cortex function and social dominance without a broader impact on autism-like behaviors. En ligne : http://dx.doi.org/10.1002/aur.2098 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=397

Reduced conditioned fear response in mice that lack Dlx1 and show subtype-specific loss of interneurons / R. MAO in Journal of Neurodevelopmental Disorders, 1-3 (September 2009)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 1-3 (September 2009) . - p.224-36 Titre : Reduced conditioned fear response in mice that lack Dlx1 and show subtype-specific loss of interneurons Type de document : Texte imprimé et/ou numérique Auteurs : R. MAO, Auteur ; Damon T. PAGE, Auteur ; I. MERZLYAK, Auteur ; C. KIM, Auteur ; L. H. TECOTT, Auteur ; P. H. JANAK, Auteur ; J. L. RUBENSTEIN, Auteur ; M. SUR, Auteur Article en page(s) : p.224-36 Langues : Anglais (eng) Mots-clés : Associative learning  Behavior  Calretinin  Fear conditioning  GABAergic  Hyperactivity  Inhibitory  Interneuron  Neuropsychiatric disease  Prepulse inhibition Index. décimale : PER Périodiques Résumé : UNLABELLED: The inhibitory GABAergic system has been implicated in multiple neuropsychiatric diseases such as schizophrenia and autism. The Dlx homeobox transcription factor family is essential for development and function of GABAergic interneurons. Mice lacking the Dlx1 gene have postnatal subtype-specific loss of interneurons and reduced IPSCs in their cortex and hippocampus. To ascertain consequences of these changes in the GABAergic system, we performed a battery of behavioral assays on the Dlx1 mutant mice, including zero maze, open field, locomotor activity, food intake, rotarod, tail suspension, fear conditioning assays (context and trace), prepulse inhibition, and working memory related tasks (spontaneous alteration task and spatial working memory task). Dlx1 mutant mice displayed elevated activity levels in open field, locomotor activity, and tail suspension tests. These mice also showed deficits in contextual and trace fear conditioning, and possibly in prepulse inhibition. Their learning deficits were not global, as the mutant mice did not differ from the wild-type controls in tests of working memory. Our findings demonstrate a critical role for the Dlx1 gene, and likely the subclasses of interneurons that are affected by the lack of this gene, in behavioral inhibition and associative fear learning. These observations support the involvement of particular components of the GABAergic system in specific behavioral phenotypes related to complex neuropsychiatric diseases. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11689-009-9025-8) contains supplementary material, which is available to authorized users. En ligne : http://dx.doi.org/10.1007/s11689-009-9025-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=341 [article] Reduced conditioned fear response in mice that lack Dlx1 and show subtype-specific loss of interneurons [Texte imprimé et/ou numérique] / R. MAO, Auteur ; Damon T. PAGE, Auteur ; I. MERZLYAK, Auteur ; C. KIM, Auteur ; L. H. TECOTT, Auteur ; P. H. JANAK, Auteur ; J. L. RUBENSTEIN, Auteur ; M. SUR, Auteur . - p.224-36. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 1-3 (September 2009) . - p.224-36 Mots-clés : Associative learning  Behavior  Calretinin  Fear conditioning  GABAergic  Hyperactivity  Inhibitory  Interneuron  Neuropsychiatric disease  Prepulse inhibition Index. décimale : PER Périodiques Résumé : UNLABELLED: The inhibitory GABAergic system has been implicated in multiple neuropsychiatric diseases such as schizophrenia and autism. The Dlx homeobox transcription factor family is essential for development and function of GABAergic interneurons. Mice lacking the Dlx1 gene have postnatal subtype-specific loss of interneurons and reduced IPSCs in their cortex and hippocampus. To ascertain consequences of these changes in the GABAergic system, we performed a battery of behavioral assays on the Dlx1 mutant mice, including zero maze, open field, locomotor activity, food intake, rotarod, tail suspension, fear conditioning assays (context and trace), prepulse inhibition, and working memory related tasks (spontaneous alteration task and spatial working memory task). Dlx1 mutant mice displayed elevated activity levels in open field, locomotor activity, and tail suspension tests. These mice also showed deficits in contextual and trace fear conditioning, and possibly in prepulse inhibition. Their learning deficits were not global, as the mutant mice did not differ from the wild-type controls in tests of working memory. Our findings demonstrate a critical role for the Dlx1 gene, and likely the subclasses of interneurons that are affected by the lack of this gene, in behavioral inhibition and associative fear learning. These observations support the involvement of particular components of the GABAergic system in specific behavioral phenotypes related to complex neuropsychiatric diseases. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11689-009-9025-8) contains supplementary material, which is available to authorized users. En ligne : http://dx.doi.org/10.1007/s11689-009-9025-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=341