Decoding the neural foundations of sexual dimorphisms in aggression: a female-centric approach

Federal Project Grant Award Summary

The National Institute of General Medical Sciences (NIGMS) awarded McLean Hospital Corporation a $2.05 million Project Grant under the Biomedical Research and Research Training program (CFDA 93.859) on September 15, 2025, with a completion date of August 31, 2029. The award funds a five-year research initiative titled "Decoding the Neural Foundations of Sexual Dimorphisms in Aggression: A Female-Centric Approach," which will be conducted at McLean Hospital's research facilities in Belmont, Massachusetts. The research leverages the Drosophila melanogaster (fruit fly) connectome to map neural circuits governing female-specific aggression, investigating how stress influences aggression through evolutionarily conserved neuropeptides and examining the developmental processes of these neural circuits.

The primary deliverables include comprehensive neural circuit mapping and characterization, investigation of stress and peptide modulation effects on female aggression, assessment of genetic modifications on key functional genes, and analysis of circuit disruptions in disease states associated with aggression dysfunction. This research is designed to advance scientific understanding of sex differences in neural mechanisms that orchestrate social behaviors and address a critical gap in knowledge regarding dysregulated aggression symptoms prevalent in neurological and psychiatric disorders that disproportionately affect women. The project builds upon prior institutional breakthroughs in identifying neurons responsible for female-specific aggression and is expected to yield insights with translational potential for understanding aggression-related pathology.

Abstract

Aggression, a fundamental behavior essential for survival and species propagation, is ubiquitous across the animal kingdom. However, the neural underpinnings of innate aggression, particularly in terms of sexual dimorphism, remain inadequately elucidated. IT is noteworthy that dysregulated aggression often surfaces as a symptom in various neurological and psychiatric disorders, with a pronounced prevalence in disorders more common among women, thereby underscoring a crucial GAP in our scientific understanding. In response to this challenge, our research is strategically focused on the female drosophila melanogaster to decipher the sexually dimorphic neural substrates governing aggression. Leveraging our prior breakthroughs in identifying neurons responsible for female-specific aggression, we have significantly enhanced the understanding of the mechanisms encoding SEX-specific primal behaviors. In the next five years, we plan to employ the fly connectome for an extensive mapping of neural circuits, aiming to elucidate how stress influences aggression via evolutionarily conserved neuropeptides and to thoroughly investigate the developmental processes of these neural circuits. Moreover, our research will delve into how these circuits are disrupted in disease states associated with aggression dysfunction. Central to our efforts is the investigation of the modulatory effects of stress and peptides on female aggression and the assessment of the consequences of genetic modifications on key functional genes. Our systematic approach to dissecting the circuitry underpinning female aggression and identifying genes related to aberrant behavior is expected to yield profound insights into the genesis of SEX differences in neural mechanisms that orchestrate social behaviors. This research program is poised to substantially advance our understanding of SEX differences in brain functions related to the regulation of aggression across diverse species.