# Gene Networks Regulating Playfulness

> **NIH NIH F31** · UNIVERSITY OF MARYLAND BALTIMORE · 2020 · $37,880

## Abstract

Project Summary
Social play, or rough-and-tumble play, is a characteristic pattern of social behavior exhibited by most mammals
during adolescence. While the function of play is debated, converging evidence finds it vital for appropriate social
behavior, cognition, and reproductive success in adulthood. Importantly, there is a sex difference in expression
of play. Males exhibit greater intensity and frequency of play than females; however, there is individual variability
in that some females play at the level of high-playing males while some males play at the level of low-playing
females. In a recent experiment, we aimed to use the power of these individual differences to gain novel insight
into sex-dependent and sex-independent transcriptional signatures associated with play. We scored play once
daily for 4 days, designating rats in the top third per sex as “high-playing” and those in the bottom third as “low-
playing”, collected tissue from the medial amygdala (MeA; site of play masculinization) for RNA-sequencing
(RNA-seq), and used Weighted Gene Co-Expression Network Analysis (WGCNA) to identify 22 gene co-
expression modules, or networks of coordinately regulated genes. Notably, all but one of the 12 modules (for
p<0.05) associated with play were sex-specific in expression, indicating a sex difference in the transcriptomic
profile associated with play in males compared to females. Building on previous theories that play’s function is
to shape circuitry enabling expression of adult behavior, our central hypothesis posits that the transcriptional
networks in the MeA underlying expression of play are sex-specific because juvenile play regulates expression
of sex-typical adult social behaviors. Using two representative sex-specific, play-associated modules, we will test
this hypothesis across 3 Specific Aims (SAs). SA1 determines whether module expression causally regulates
playfulness in a sex-specific manner. In this aim, we will test the effect of overexpressing module regulators from
our representative sex-specific modules in the MeA and determine whether this affects play in the predicted sex
only. SA2 correlates expression of juvenile play with expression of sex-typical adult social behavior, determining
if individual differences in playfulness track to differences in expression of territorial aggression (males) and
maternal behavior (females). Finally, SA3 determines whether module expression causally regulates expression
of sex-typical adult social behavior. As in SA1, we will induce expression of our representative sex-specific
modules. We will then determine whether this is sufficient to increase expression of two sex-typical adult social
behaviors, maternal behavior and territorial aggression as in SA2, in the absence of play. My sponsor is Dr.
Margaret McCarthy, a leader in the field of brain sex differences, and my co-sponsor is Dr. Seth Ament, an expert
in the functional genomics of social behavior. With their guidance, as well as ...

## Key facts

- **NIH application ID:** 10065110
- **Project number:** 1F31MH123025-01A1
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Ashley Marquardt
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $37,880
- **Award type:** 1
- **Project period:** 2020-07-26 → 2022-07-25

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10065110

## Citation

> US National Institutes of Health, RePORTER application 10065110, Gene Networks Regulating Playfulness (1F31MH123025-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10065110. Licensed CC0.

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