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Sex-Specific Social Behavior and Amygdala Proteomic Deficits in Foxp2 ^+/- Mutant Mice.

ABSTRACT: 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.

SUBMITTER: Herrero MJ

PROVIDER: S-EPMC8374433 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Social play is a frequently studied behavior and it is the most characteristic form of social interaction observed in adolescent rats. Social play is necessary for adolescents to develop proper cognitive, emotional, and social competency. Deficits in social play have been observed in several neurodegenerative disorders such as autism, schizophrenia, and attention deficit hyperactivity disorder. However, the information available on neural substrates and the mechanism involved in social play is still limited. This study characterized social play by proteomic and transcriptional profiling studies. Social play was performed on male Sprague Dawley rats on postnatal day 38 and protein and gene expression in the amygdala was determined following behavioral testing. The proteomic analysis led to the identification of 170 differentially expressed proteins (p≤0.05) with 67 upregulated and 103 downregulated proteins. The transcriptomic analysis led to the identification of 188 genes (adjusted p≤0.05) with 55 upregulated and 133 downregulated genes. Based on both protein and gene expression data, DAVID analysis revealed that social play altered neurotransmitter signaling including GABAergic and glutamatergic signaling and G-protein coupled receptor (GPCR) signaling. These data suggest that the synaptic levels of GABA and glutamate increased during play. Ingenuity Pathway Analysis (IPA) confirmed these alterations. IPA also revealed that differentially expressed genes/proteins in our data had significant over representation of additional neurotransmitter signaling systems, including the opioid, serotonin, and dopamine systems, suggesting that play alters the systems involved in the regulation of reward. In addition, corticotropin-releasing hormone signaling was altered indicating that an increased level of stress occurs during play. Our data suggest that increased inhibitory GPCR signaling in these neurotransmitter pathways occurs following social play as a physiological response to regulate the induced level of reward and stress and to maintain the excitatory-inhibitory balance in the neurotransmitter systems.

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Sex-Specific Social Behavior and Amygdala Proteomic Deficits in Foxp2 ^+/- Mutant Mice.

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OmicsDI is part of the ELIXIR infrastructure

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Dataset Information

Sex-Specific Social Behavior and Amygdala Proteomic Deficits in Foxp2 +/- Mutant Mice.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Sex-Specific Social Behavior and Amygdala Proteomic Deficits in Foxp2 ^+/- Mutant Mice.