scholarly journals Sex-Specific Social Behavior and Amygdala Proteomic Deficits in Foxp2+/− Mutant Mice

2021 ◽  
Vol 15 ◽  
Author(s):  
Maria Jesus Herrero ◽  
Li Wang ◽  
David Hernandez-Pineda ◽  
Payal Banerjee ◽  
Heidi Y. Matos ◽  
...  
Keyword(s):  
Social Behavior ◽  
Social Interactions ◽  
Social Behaviors ◽  
Autism Spectrum ◽  
Loss Of Function ◽  
Neuronal Communication ◽  
Males And Females ◽  
Spectrum Disorders ◽  
Encoding Gene ◽  
Dopamine Signaling

In humans, mutations in the transcription factor encoding gene, FOXP2, are associated with language and Autism Spectrum Disorders (ASD), the latter characterized by deficits in social interactions. However, little is known regarding the function of Foxp2 in male or female social behavior. Our previous studies in mice revealed high expression of Foxp2 within the medial subnucleus of the amygdala (MeA), a limbic brain region highly implicated in innate social behaviors such as mating, aggression, and parental care. Here, using a comprehensive panel of behavioral tests in male and female Foxp2+/– heterozygous mice, we investigated the role Foxp2 plays in MeA-linked innate social behaviors. We reveal significant deficits in olfactory processing, social interaction, mating, aggressive, and parental behaviors. Interestingly, some of these deficits are displayed in a sex-specific manner. To examine the consequences of Foxp2 loss of function specifically in the MeA, we conducted a proteomic analysis of microdissected MeA tissue. This analyses revealed putative sex differences expression of a host of proteins implicated in neuronal communication, connectivity, and dopamine signaling. Consistent with this, we discovered that MeA Foxp2-lineage cells were responsive to dopamine with differences between males and females. Thus, our findings reveal a central and sex-specific role for Foxp2 in social behavior and MeA function.

scholarly journals Towards a gene-level map of resilience to genetic variants associated with autism

2021 ◽  
Author(s):  
Thomas Rolland ◽  
Freddy Cliquet ◽  
Richard J.L. Anney ◽  
Nicolas Traut ◽  
Alexandre Mathieu ◽  
...  
Keyword(s):  
Genetic Data ◽  
Autism Spectrum ◽  
Common Variants ◽  
Loss Of Function ◽  
Polygenic Scores ◽  
Gene Level ◽  
Clinical Profiles ◽  
Males And Females ◽  
Spectrum Disorders ◽  
Genetic Profiles

ABSTRACTWhile over 100 genes are now significantly associated with autism spectrum disorders (ASD), the penetrance of the variants affecting these genes remains poorly understood. Here, we quantified the prevalence of rare loss-of-function (LoF) mutations affecting 156 genes robustly associated with ASD (SPARK genes) using genetic data from more than 10,000 individuals with ASD and 100,000 undiagnosed individuals. We then investigated the clinical, brain imaging and genetic profiles of individuals heterozygous for these rare deleterious variants who were not diagnosed with ASD. These “resilient” individuals, observed in less than 1% of the general population, were equally distributed among males and females, but displayed low polygenic scores for ASD compared to LoF heterozygotes diagnosed with ASD. The interplay between rare and common variants may therefore contribute to the clinical profiles of the individuals carrying LoF in genes associated with ASD.

scholarly journals Does microglial dysfunction play a role in autism and Rett syndrome?

2011 ◽  
Vol 7 (1) ◽  
pp. 85-97 ◽  
Author(s):  
Izumi Maezawa ◽  
Marco Calafiore ◽  
Heike Wulff ◽  
Lee-Way Jin
Keyword(s):  
Social Interactions ◽  
Rett Syndrome ◽  
Autism Spectrum ◽  
Developmental Trajectory ◽  
Repetitive Behaviors ◽  
Environmental Toxins ◽  
Communication Difficulties ◽  
Brain Circuitry ◽  
Spectrum Disorders

Autism spectrum disorders (ASDs) including classic autism is a group of complex developmental disabilities with core deficits of impaired social interactions, communication difficulties and repetitive behaviors. Although the neurobiology of ASDs has attracted much attention in the last two decades, the role of microglia has been ignored. Existing data are focused on their recognized role in neuroinflammation, which only covers a small part of the pathological repertoire of microglia. This review highlights recent findings on the broader roles of microglia, including their active surveillance of brain microenvironments and regulation of synaptic connectivity, maturation of brain circuitry and neurogenesis. Emerging evidence suggests that microglia respond to pre- and postnatal environmental stimuli through epigenetic interface to change gene expression, thus acting as effectors of experience-dependent synaptic plasticity. Impairments of these microglial functions could substantially contribute to several major etiological factors of autism, such as environmental toxins and cortical underconnectivity. Our recent study on Rett syndrome, a syndromic autistic disorder, provides an example that intrinsic microglial dysfunction due to genetic and epigenetic aberrations could detrimentally affect the developmental trajectory without evoking neuroinflammation. We propose that ASDs provide excellent opportunities to study the influence of microglia on neurodevelopment, and this knowledge could lead to novel therapies.

scholarly journals Neonatal Exposure to Sevoflurane Induces Abnormal Social Behaviors and Deficits in Fear Conditioning in Mice

2009 ◽  
Vol 110 (3) ◽  
pp. 628-637 ◽  
Author(s):  
Maiko Satomoto ◽  
Yasushi Satoh ◽  
Katsuo Terui ◽  
Hideki Miyao ◽  
Kunio Takishima ◽  
...  
Keyword(s):  
Social Interaction ◽  
Social Behavior ◽  
Fear Conditioning ◽  
Social Behaviors ◽  
Autism Spectrum ◽  
Social Recognition ◽  
Neonatal Exposure ◽  
Learning Deficits ◽  
Neonatal Mice ◽  
The Social

Background Neonatal exposure to anesthetics that block N-methyl-D-aspartate receptors and/or hyperactivate gamma-aminobutyric acid type A receptor has been shown to cause neuronal degeneration in the developing brain, leading to functional deficits later in adulthood. The authors investigated whether exposure of neonatal mice to inhaled sevoflurane causes deficits in social behavior as well as learning disabilities. Methods Six-day-old C57BL/6 mice were exposed to 3% sevoflurane for 6 h. Activated cleaved caspase-3 immunohistochemical staining was used for detection of apoptosis. Cognitive functions were tested by pavlovian conditioned fear test. Social behavior was tested by social recognition and interaction tests. Results Neonatal exposure to sevoflurane significantly increased the number of apoptotic cells in the brain immediately after anesthesia. It caused persistent learning deficits later in adulthood as evidenced by decreased freezing response in both contextual and cued fear conditioning. The social recognition test demonstrated that mice with neonatal exposure to sevoflurane did not develop social memory. Furthermore, these mice showed decreased interactions with a social target compared with controls in the social interaction test, indicating a social interaction deficit. The authors did not attribute these abnormalities in social behavior to impairments of general interest in novelty or olfactory sensation, because they did not detect significant differences in the test for novel inanimate object interaction or for olfaction. Conclusions This study shows that exposure of neonatal mice to inhaled sevoflurane could cause not only learning deficits but also abnormal social behaviors resembling autism spectrum disorder.

scholarly journals Abnormal social behaviors and dysfunction of autism-related genes associated with daily agonistic interactions in mice

2017 ◽  
Author(s):  
Natalia N. Kudryavtseva ◽  
Irina L. Kovalenko ◽  
Dmitry A. Smagin ◽  
Anna G. Galyamina ◽  
Vladimir N. Babenko
Keyword(s):  
Social Behavior ◽  
Social Environment ◽  
Social Behaviors ◽  
Brain Regions ◽  
Autistic Spectrum Disorders ◽  
Male Mice ◽  
Agonistic Interactions ◽  
Autistic Spectrum ◽  
Spectrum Disorders ◽  
The Brain

AbstractBackgroundThe ability of people to communicate with each other is a necessary component of social behavior and the normal development of individuals who live in a community. An apparent decline in sociability may be the result of a negative social environment or the development of affective and neurological disorders, including autistic spectrum disorders. The behavior of these humans may be characterized by the deterioration of socialization, low communication, and repetitive and restricted behaviors. This study aimed to analyze changes in the social behaviors of male mice induced by daily agonistic interactions and investigate the involvement of genes, related with autistic spectrum disorders in the process of the impairment of social behaviors.MethodsAbnormal social behavior is induced by repeated experiences of aggression accompanied by wins (winners) or chronic social defeats (losers) in daily agonistic interactions in male mice. The collected brain regions (the midbrain raphe nuclei, ventral tegmental area, striatum, hippocampus, and hypothalamus) were sequenced at JSC Genoanalytica (http://genoanalytica.ru/, Moscow, Russia). The Cufflinks program was used to estimate the gene expression levels. Bioinformatic methods were used for the analysis of differentially expressed genes in male mice.ResultsThe losers exhibited an avoidance of social contacts toward unfamiliar conspecific, immobility and low communication on neutral territory. The winners demonstrated aggression and hyperactivity in this condition. The exploratory activity (rearing) and approaching behavior time towards the partner were decreased, and the number of episodes of repetitive self-grooming behavior was increased in both social groups. These symptoms were similar to the symptoms observed in animal models of autistic spectrum disorders. In an analysis of the RNA-Seq database of the whole transcriptome in the brain regions of the winners and losers, we identified changes in the expression of the following genes, which are associated with autism in humans: Tph2, Maoa, Slc6a4, Htr7,Gabrb3, Nrxn1, Nrxn2, Nlgn1, Nlgn2, Nlgn3, Shank2, Shank3, Fmr1, Ube3a, Pten, Cntn3, Foxp2, Oxtr, Reln, Cadps2, Pcdh10, Ctnnd2, En2, Arx, Auts2, Mecp2, and Ptchd1.Common and specific changes in the expression of these genes in different brain regions were identified in the winners and losers.ConclusionsThis research demonstrates for the first time that abnormalities in social behaviors that develop under a negative social environment in adults may be associated with alterations in expression of genes, related with autism in the brain.

scholarly journals Sex- and context-dependent effects of acute isolation on vocal and non-vocal social behaviors in mice

PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0255640
Author(s):  
Xin Zhao ◽  
Patryk Ziobro ◽  
Nicole M. Pranic ◽  
Samantha Chu ◽  
Samantha Rabinovich ◽  
...  
Keyword(s):  
Social Behavior ◽  
Social Interactions ◽  
Social Isolation ◽  
Social Behaviors ◽  
Social Motivation ◽  
Same Sex ◽  
Female Mice ◽  
The Social ◽  
Opposite Sex ◽  
Brain And Behavior

Humans are extraordinarily social, and social isolation has profound effects on our behavior, ranging from increased social motivation following short periods of social isolation to increased anti-social behaviors following long-term social isolation. Mice are frequently used as a model to understand how social isolation impacts the brain and behavior. While the effects of chronic social isolation on mouse social behavior have been well studied, much less is known about how acute isolation impacts mouse social behavior and whether these effects vary according to the sex of the mouse and the behavioral context of the social encounter. To address these questions, we characterized the effects of acute (3-day) social isolation on the vocal and non-vocal social behaviors of male and female mice during same-sex and opposite-sex social interactions. Our experiments uncovered pronounced effects of acute isolation on social interactions between female mice, while revealing more subtle effects on the social behaviors of male mice during same-sex and opposite-sex interactions. Our findings advance the study of same-sex interactions between female mice as an attractive paradigm to investigate neural mechanisms through which acute isolation enhances social motivation and promotes social behavior.

scholarly journals Neural Circuits for Social Interactions: From Microcircuits to Input-Output Circuits

2021 ◽  
Vol 15 ◽  
Author(s):  
Sen Xu ◽  
Ming Jiang ◽  
Xia Liu ◽  
Yahan Sun ◽  
Liang Yang ◽  
...  
Keyword(s):  
Social Behavior ◽  
Social Interactions ◽  
Molecular Mechanisms ◽  
Social Preference ◽  
Neural Circuits ◽  
Social Behaviors ◽  
Social Cues ◽  
Input Output ◽  
Social Exploration ◽  
Pathological Development

Social behaviors entail responses to social information and requires the perception and integration of social cues through a complex cognition process that involves attention, memory, motivation, and emotion. Neurobiological and molecular mechanisms underlying social behavior are highly conserved across species, and inter- and intra-specific variability observed in social behavior can be explained to large extent by differential activity of a conserved neural network. However, neural microcircuits and precise networks involved in social behavior remain mysterious. In this review, we summarize the microcircuits and input-output circuits on the molecular, cellular, and network levels of different social interactions, such as social exploration, social hierarchy, social memory, and social preference. This review provides a broad view of how multiple microcircuits and input-output circuits converge on the medial prefrontal cortex, hippocampus, and amygdala to regulate complex social behaviors, as well as a potential novel view for better control over pathological development.

scholarly journals Characterizing Daily-Life Social Interactions in Adolescents and Young Adults with Neurodevelopmental Disorders: A Comparison Between Individuals with Autism Spectrum Disorders and 22q11.2 Deletion Syndrome

2022 ◽  
Author(s):  
Clémence Feller ◽  
Laura Ilen ◽  
Stephan Eliez ◽  
Maude Schneider
Keyword(s):  
Autism Spectrum Disorders ◽  
Social Interactions ◽  
Subjective Experience ◽  
Daily Life ◽  
22Q11.2 Deletion Syndrome ◽  
Autism Spectrum ◽  
Mobile App ◽  
Deletion Syndrome ◽  
22Q11.2 Deletion ◽  
Spectrum Disorders

AbstractSocial impairments are common features of 22q11.2 deletion syndrome (22q11DS) and autism spectrum disorders (ASD). The Ecological Momentary Assessment (EMA) allowed access to daily-life information in order to explore the phenomenology of social interactions. 32 individuals with 22q11DS, 26 individuals with ASD and 44 typically developing peers (TD) aged 12–30 were assessed during 6 days 8 times a day using a mobile app. Participants with 22q11DS and ASD did not spend more time alone but showed distinct implication in the social sphere than TD. Distinct profiles emerged between the two conditions regarding the subjective experience of aloneness and the subjective experience of social interactions. This study highlights distinct social functioning profiles in daily-life in 22q11DS and ASD that points towards different therapeutic targets.

scholarly journals Characterizing daily-life social interactions in adolescents and young adults with neurodevelopmental disorders: a comparison between individuals with Autism Spectrum Disorders and 22q11.2 deletion syndrome

2021 ◽  
Author(s):  
Clémence Mathilde Feller ◽  
Laura Ilen ◽  
Maude Schneider
Keyword(s):  
Autism Spectrum Disorders ◽  
Social Interactions ◽  
Subjective Experience ◽  
Daily Life ◽  
22Q11.2 Deletion Syndrome ◽  
Autism Spectrum ◽  
Deletion Syndrome ◽  
22Q11.2 Deletion ◽  
Social Impairments ◽  
Spectrum Disorders

Abstract Background: Social impairments are common features of several neurodevelopmental conditions, including 22q11.2 deletion syndrome (22q11DS) and autism spectrum disorders (ASD). However, little is known about social interactions in daily-life. The Ecological Momentary Assessment (EMA) was used to have access to daily-life information and to distinguish the phenomenology of social interactions between the two conditions, often considered as presenting a similar profile of social impairments.Methods: 32 individuals with 22q11DS, 26 individuals with ASD and 44 healthy controls (HC) aged 12-30 were recruited. All participants were assessed during 6 days 8 times a day using a mobile app. The EMA protocol assessed positive and negative affect, social context (alone versus in company) and the subjective experience of aloneness and social interactions.Results: Participants with 22q11DS and ASD did not spend more time alone, but spent less time with familiar individuals such as friends, and more time with people they live with, compared to HC. However, distinct profiles emerged between the two conditions regarding the subjective experience of aloneness, with more intense feelings of exclusion in participants with ASD compared to participants with 22q11DS and HC. The subjective appreciation of interactions revealed that individuals with ASD felt more judged and more nervous than both 22q11DS and HC. Nevertheless, both conditions expressed a higher desire to be alone when in company of other people than HC.Conclusions: This study highlights distinct social functioning profiles in daily-life in 22q11DS and ASD, giving new intel regarding the social phenotype in these conditions, and pointing towards different therapeutic targets.

scholarly journals Rat ultrasonic vocalizations and novelty-induced social and non-social investigation behavior in a seminatural environment

2021 ◽  
Author(s):  
Indrek Heinla ◽  
Xi Chu ◽  
Anders Agmo ◽  
Eelke Snoeren
Keyword(s):  
Social Behavior ◽  
Social Interactions ◽  
Social Behaviors ◽  
Ultrasonic Vocalizations ◽  
Sensory Cues ◽  
Social Investigation ◽  
Wide Range ◽  
Vocal Signals ◽  
Transfer Of Information

Although rats are known to emit ultrasonic vocalizations (USVs), it remains unclear whether these calls serve an auditory communication purpose. For USVs to be part of communication, the vocal signals will need to be a transfer of information between two or more conspecifics, and with the possibility to induce changes in the behavior of the recipient. Therefore, the aim of our study was to investigate the role of USVs in rats' social and non-social investigation strategies when introduced into a large novel environment with unfamiliar conspecifics. We quantified a wide range of social and non-social behaviors in the seminatural environment, which could be affected by subtle signals, including USVs. We found that during the first hour in the seminatural environment the ability to vocalize did not affect how quickly rats met each other, their overall social investigation behavior, their passive social behavior nor their aggressive behavior. Furthermore, the non-social exploratory behaviors and behaviors reflecting anxiety/stress-like states were also unaffected. These results demonstrated that a disability to vocalize did not result in significant disadvantages (or changes) compared to intact conspecifics regarding social and non-social behaviors. This suggests that other (multi)sensory cues are more relevant in social interactions than USVs.

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