Project description:Social behaviors, including behaviors directed toward young offspring, exhibit striking sex differences. Understanding how these sexually dimorphic behaviors are regulated at the level of circuits and transcriptomes will provide insights into neural mechanisms of sex-specific behaviors. Here, we uncover a sexually dimorphic role of the medial amygdala (MeA) in governing parental and infanticidal behaviors. Contrary to traditional views, activation of GABAergic neurons in the MeA promotes parental behavior in females, while activation of this population in males differentially promotes parental versus infanticidal behavior in an activity-level-dependent manner. Through single-cell transcriptomic analysis, we found that molecular sex differences in the MeA are specifically represented in GABAergic neurons. Collectively, these results establish crucial roles for the MeA as a key node in the neural circuitry underlying pup-directed behaviors and provide important insight into the connection between sex differences across transcriptomes, cells, and circuits in regulating sexually dimorphic behavior.
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.
Project description:In humans, mutations in the transcription factor encoding gene, FOXP2, are associated with language and Autism Spectrum (ASD) Disorders, 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 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 and found sex differences in 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.
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.
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.
Project description:This project examined if sex differences in K48 polyubiquitination in the amygdala were developmentally regulated. This used basolateral amygdala (BLA) samples collected from 4 and 9 week old male and female Sprague-Dawley rats.
Project description:This project examined sex differences in the role of protein sumoylation in the amygdala during context fear memory formation in male and female rats.
Project description:This project examined sex differences in the role of K63 polyubiquitination in the amygdala during context fear memory formation in male and female rats.
