Summary: Researchers will pinpoint which elements of social behavior are regulated by androgens and determine the cellular and molecular mechanisms behind that regulation.
Source: University of Houston
Most people recognize testosterone as an androgen linked to male physiology and behavior — influencing libido, aggression, and mood — but the detailed mechanisms by which it and related hormones shape social behavior remain unclear.
With a $1.9 million grant from the National Institute of General Medical Sciences, Beau Alward, an assistant professor of psychology with a joint appointment in biology at the University of Houston, will pursue experiments designed to clarify how androgens act on the brain to control social traits.
“We know androgens like testosterone control social behavior, but we still do not know precisely which aspects of social behavior they regulate and how they do it,” Alward said. “We understand that androgens influence neurons, but the specific cellular and molecular pathways remain to be defined.”
Alward’s team will study the highly social African cichlid fish Astatotilapia burtoni (A. burtoni), taking advantage of its well-characterized social hierarchies and visible status-related traits. The project combines advanced approaches—single-cell genomics to measure gene expression at cellular resolution, whole-brain imaging to map active neural circuits, and ethologically rich social behavior paradigms to observe natural interactions—to link hormones, genes, and neural activity to behavior.
Disentangling steroid hormone effects on brain function is difficult because these hormones influence many physiological systems at once, producing both direct and indirect consequences for behavior. Alward’s strategy uses genetic and pharmacological tools to isolate direct androgen signaling pathways in order to separate them from downstream, indirect effects.
Using CRISPR/Cas9 gene editing, Alward generated A. burtoni mutants lacking specific androgen receptors (ARs). Some fish lack a functional ARα gene, others lack ARβ, and a subset lack both receptors. These receptor-specific mutants provide a rare opportunity to determine which receptor mediates particular physiological and behavioral components of social status.
The mutant phenotypes already reveal distinct roles for the two receptors. “ARα mutant males do not perform dominant social behaviors but retain large testes and bright coloration, while ARβ mutant males continue to show dominant behaviors but have small testes and muted coloration,” Alward explained. “Males lacking both receptors lose those dominant traits entirely and display behaviors more typical of females.”
Alward will combine these AR-mutant fish with targeted pharmacology and social contexts that challenge the neural systems controlling social decisions. Naturalistic social paradigms will reveal how specific genes and neurons contribute to behavior under real-world conditions, and single-cell genomics will identify the gene expression changes in defined cell types. Whole-brain imaging will map the circuits and neural activity patterns associated with those gene expression profiles and behavioral states.
By integrating genetic manipulation, cellular-resolution gene expression, brain-wide activity mapping, and careful behavioral observation, the project aims to uncover the molecular and neural architecture through which androgens regulate social behavior. The approach will illuminate how steroid hormones shape gene expression in the brain and drive neuroplasticity—the brain’s ability to change and adapt in response to social experiences.
Because these AR mutants are unique to Alward’s laboratory, the research program occupies a special niche for addressing fundamental questions about hormonal control of the brain. “No other laboratory currently possesses these AR mutants, so we are in a unique position to tackle these questions,” Alward said. “This work will allow us to address core issues about how hormones influence neural circuits and behavior.”
Answers from this work may also inform broader questions about how hormonal systems shape social behavior across species, including potential parallels in mammals and humans, and how social systems evolve over time. While the direct translation to human behavior requires further study, identifying conserved cellular and molecular mechanisms could help frame future research on hormone-brain-behavior links in other animals.
About this neuroscience research news
Author: Laurie Fickman ([email protected])
Source: University of Houston
Contact: Laurie Fickman – University of Houston
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