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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)
[article]
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
in Autism Research > 12-5 (May 2019) . - p.732-743[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 Inferring power and dominance from dyadic nonverbal interactions in autism spectrum disorder / M. KUSCHEFSKI in Autism Research, 12-3 (March 2019)
[article]
Titre : Inferring power and dominance from dyadic nonverbal interactions in autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : M. KUSCHEFSKI, Auteur ; C. M. FALTER-WAGNER, Auteur ; Gary BENTE, Auteur ; Kai VOGELEY, Auteur ; Alexandra Livia GEORGESCU, Auteur Article en page(s) : p.505-516 Langues : Anglais (eng) Mots-clés : autism spectrum disorder dominance dyadic social interaction nonverbal communication power submissiveness Index. décimale : PER Périodiques Résumé : Research studies to date have revealed conflicting results with respect to the processing of nonverbal cues from social interactions in autism spectrum disorder (ASD). Therefore, the aim of the present study was to investigate the contribution of two important factors for the perception of dyadic social interactions, namely (a) the movement contingency and (b) the spatial context. To this end, 26 adult participants with ASD and 26 age-, sex-, and IQ-matched typically developed control participants observed animations presenting nonverbal interactions between two human virtual characters enacting power relationships. We manipulated (a) movement contingency by exchanging one of the two original agents with an agent from another dyad and (b) spatial context by changing agents' spatial orientation to a back-to-back position. Participants were asked to rate dominance and submissiveness of these agents. Results showed that the movement contingency manipulation affected accuracy and consistency of power perception and that the spatial context manipulation slowed down reaction times comparably in both groups. With regard to group differences, individuals with ASD were found to judge power relationships slower compared to control participants, potentially suggesting a more explicit processing style in ASD. Furthermore, the spatial context manipulation slowed down the reaction times more in the contingent compared to the non-contingent conditions only in the ASD group. These findings contribute to the ongoing debate whether individuals with ASD have difficulties in understanding nonverbal cues in a dyadic context by suggesting that they do so in more subtle ways than previously investigated. Autism Res 2019, 12: 505-516 (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: This study shows that the ability and speed of judging who is dominant in a social interaction depends on two factors: (a) whether their movements are matched and (b) whether they are facing each other or not. This is similarly the case for participants with and without autism. Interestingly, however, individuals with autism seem to judge generally slower, suggesting a more explicit processing style. The two factors seem to interact, suggesting that nonverbal processing difficulties are subtler than previously thought. En ligne : http://dx.doi.org/10.1002/aur.2069 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=387
in Autism Research > 12-3 (March 2019) . - p.505-516[article] Inferring power and dominance from dyadic nonverbal interactions in autism spectrum disorder [Texte imprimé et/ou numérique] / M. KUSCHEFSKI, Auteur ; C. M. FALTER-WAGNER, Auteur ; Gary BENTE, Auteur ; Kai VOGELEY, Auteur ; Alexandra Livia GEORGESCU, Auteur . - p.505-516.
Langues : Anglais (eng)
in Autism Research > 12-3 (March 2019) . - p.505-516
Mots-clés : autism spectrum disorder dominance dyadic social interaction nonverbal communication power submissiveness Index. décimale : PER Périodiques Résumé : Research studies to date have revealed conflicting results with respect to the processing of nonverbal cues from social interactions in autism spectrum disorder (ASD). Therefore, the aim of the present study was to investigate the contribution of two important factors for the perception of dyadic social interactions, namely (a) the movement contingency and (b) the spatial context. To this end, 26 adult participants with ASD and 26 age-, sex-, and IQ-matched typically developed control participants observed animations presenting nonverbal interactions between two human virtual characters enacting power relationships. We manipulated (a) movement contingency by exchanging one of the two original agents with an agent from another dyad and (b) spatial context by changing agents' spatial orientation to a back-to-back position. Participants were asked to rate dominance and submissiveness of these agents. Results showed that the movement contingency manipulation affected accuracy and consistency of power perception and that the spatial context manipulation slowed down reaction times comparably in both groups. With regard to group differences, individuals with ASD were found to judge power relationships slower compared to control participants, potentially suggesting a more explicit processing style in ASD. Furthermore, the spatial context manipulation slowed down the reaction times more in the contingent compared to the non-contingent conditions only in the ASD group. These findings contribute to the ongoing debate whether individuals with ASD have difficulties in understanding nonverbal cues in a dyadic context by suggesting that they do so in more subtle ways than previously investigated. Autism Res 2019, 12: 505-516 (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: This study shows that the ability and speed of judging who is dominant in a social interaction depends on two factors: (a) whether their movements are matched and (b) whether they are facing each other or not. This is similarly the case for participants with and without autism. Interestingly, however, individuals with autism seem to judge generally slower, suggesting a more explicit processing style. The two factors seem to interact, suggesting that nonverbal processing difficulties are subtler than previously thought. En ligne : http://dx.doi.org/10.1002/aur.2069 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=387