Adolescent Social Isolation Reprograms the Medial Amygdala: Transcriptome and Sex Differences in Reward
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ABSTRACT:
PROVIDER: PRJNA610626 | ENA |
REPOSITORIES: ENA
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Project description:Adolescence is a sensitive window for reward- and stress-associated behavior. Although stress during this period causes long-term changes in behavior in males, how females respond is relatively unknown. Here we show that social isolation stress in adolescence, but not adulthood, induces persistent but opposite effects on anxiety- and cocaine-related behaviors in male vs. female mice, and that these effects are reflected in transcriptional profiles within the adult medial amygdala (meA). By integrating differential gene expression with co-expression network analyses, we identified crystallin mu (Crym), a thyroid hormone binding protein, as a key driver of these transcriptional profiles. Manipulation of Crym specifically within adult meA neurons recapitulates the behavioral and transcriptional effects of social isolation and re-opens a window of plasticity that is otherwise closed. Our results establish that meA is essential for sex-specific responses to stressful and rewarding stimuli through transcriptional programming that occurs during adolescence.
2020-11-30 | GSE146472 | GEO
Project description:A substantial proportion of basal amygdala (BA) glutamate neurons project to nucleus accumbens (NAc). The evidence that these neurons are activated by reward and/or aversion is equivocal. Social stimuli are highly salient, and in male mice we conducted a detailed analysis of the responsiveness of BA-NAc neurons to estrous female (social reward, SR) or aggressive male (social aversion, SA). Both SR and SA activated c-Fos expression in a relatively high number of BA-NAc neurons in intermediate (int) BA. Using Fos-TRAP2 mice, the majority of social int-BA-NAc neurons were activated by either SR or SA, i.e. were monovalent, and in similar numbers. Fiber photometry provided corroborative evidence that int-BA-NAc neural pathway activity was similar in response to SR or SA. These findings contribute substantially to understanding the topography and valence-specificity of BA-NAc neurons with respect to highly salient stimuli, and to identifying molecular targets for treatment of reward- or aversion-specific psychopathologies.
2023-12-17 | GSE220269 | GEO
Project description:Social isolation poses a severe mental and physiological burden on humans. Most animal models that investigate this effect are based on prolonged isolation, which does not mimic the milder conditions experienced by people in the real world. Here we show that in the medial amygdala, a brain structure that is crucial for social memory, acute social isolation causes social memory loss and significant changes in specific mRNAs and proteins.
2021-11-03 | PXD026871 | Pride
Project description:Single-cell RNA sequencing of male and female mouse medial amygdala using Drop-Seq
2019-02-14 | GSE124061 | GEO
Project description:Social play was performed on one cohort of adolescent rats. Other cohort was remaining naïve to behavioral testing. The rats were scarified following behavioral testing on postnatal day 38. Amygdala was isolated form the brain, homogenized the tissue, proteins were quantified, trypsin digested, and analyzed by LC ESI MS/MS.
2019-11-06 | PXD012677 | Pride
Project description:Little is known about how Kiss1 cells in the medial amygdala (MeA) are regulated and what other gene transcripts are produced by MeA Kiss1 neurons. Estradiol upregulates Kiss1 expression in the medial amygdala (MeA), but it remains unknown if estradiol regulates other gene transcripts in MeA Kiss1 cells. The goal of this study is to identify novel gene transcripts produced by MeA Kiss1 cells and to determine how estradiol regulates the expression of these transcripts. We selectively isolated mRNA from Kiss1 cells in the MeA of female mice using Ribotag transgenic mice, immunoprecipitation, and RNA-seq. Over 13,000 gene transcripts produced by MeA Kiss1 cells were identified, but only 45 of these transcripts had expression levels altered by estradiol.
2023-02-13 | GSE224788 | GEO
Project description:The objective of this study was to determine changes in gene expression within the extended amygdala following binge-like alcohol drinking by adolescent alcohol-preferring (P) rats. Starting at 28 days of age, P rats were given concurrent access to 15 and 30 % ethanol for 3 one-h sessions for 5 consecutive days each week until they were 49 days old. Rats were killed by decapitation 3 h after the first ethanol access session on the 15th day of drinking. RNA was prepared from micropunch samples of the nucleus accumbens shell (Acb-sh) and central nucleus of the amygdala (CeA). Ethanol intakes were 2.5 to 3.0 g/kg/session. There were 154 and 182 unique named genes that significantly differed (FDR = 0.2) between the water and ethanol group in the Acb-sh and CeA, respectively. Gene Ontology (GO) analyses indicated that adolescent binge drinking produced changes in the in biological processes involved in cell proliferation and regulation of cellular structure in the Acb-sh, and in neuron projection and positive regulation of cellular organization in the CeA. Ingenuity Pathway Analysis indicated that, in the Acb-sh, there were several major intracellular signaling pathways (e.g., cAMP-mediated and protein kinase A signaling pathways) altered by adolescent drinking, with 3-fold more genes up-regulated than down-regulated in the alcohol group. The cAMP-mediated signaling system was also up-regulated in the CeA of the alcohol group. Weighted gene co-expression network analysis (WGCNA) indicated significant G-protein coupled receptor signaling and transmembrane receptor protein kinase signaling categories in the Acb-sh and CeA, respectively. Overall, the results of this study indicated that binge-like alcohol drinking by adolescent P rats is differentially altering the expression of genes in the Acb-sh and CeA, some of which are involved in intracellular signaling pathways and may produce long-term changes in neuronal function. Differences in gene expression in the central nucleus of the amygdala (CeA) were compared in two groups of alcohol-preferring (P) rats, one given water only and the other given access to 15 & 30% ethanol during adolescence.
2013-07-20 | E-GEOD-49040 | biostudies-arrayexpress
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.
2019-11-04 | GSE126023 | GEO
Project description:Sexually Dimorphic Control of Parenting Behavior by the Medial Amygdala
| PRJNA510633 | ENA
Project description:Adolescent stress can impact health and well-being not only during adulthood of the exposed individual but even in future generations. To begin to unravel the molecular mechanisms underlying these long-term effects, we determined if stress administered to males during adolescence (F0) altered anxiety behaviors and gene expression profiles in the amygdala – a critical region in the control of emotional states – of their progeny in two generations (F1, F2). Male C57BL/6 mice underwent chronic unpredictable stress (CUS) for two-weeks during adolescence and were used to produce two generations of offspring. Male and female F1 and F2 animals were tested in behavioral assays to measure affective behavior and stress reactivity. Remarkably, transgenerational inheritance of paternal stress exposure produced a protective phenotype in the male, but not the female lineage. In behaviorally naïve mice (n = 5), mRNA from the amygdala was sequenced to determine the total transcriptomes and pathway analysis was employed to identify differentially expressed genes of functional interest. RNA-Seq analysis of the amygdala from F1 and F2 male offspring identified genes with altered expression in mice derived from fathers exposed to CUS. Among the differentially expressed pathway was ‘notch signaling’, which was significantly altered in F2 males. Therefore, we show that paternal stress exposure impacts future generations which manifest in behavioral changes and molecular adaptations.
2018-12-19 | GSE108452 | GEO