Early life stress is one of the strongest predictors of persistent behavioral dysregulation later in life, yet the brain mechanisms that lock in these changes remain unclear. A growing body of evidence points to glutamate—the brain’s primary excitatory neurotransmitter—as a key driver of how stressful experiences reshape neural circuits.
This project investigates how early life stress alters glutamatergic signaling to produce long-lasting changes in aggression-related brain pathways. Using preclinical models, we focus on NMDA receptor–dependent plasticity within limbic and hypothalamic circuits that regulate threat and social behavior. Our work shows that stressful experiences during development sensitize these circuits, biasing them toward heightened and persistent aggression.
Importantly, we find that pharmacological agents targeting glutamate receptors can have opposing effects depending on context. While some NMDA receptor antagonists suppress stress-induced aggression, others—such as ketamine—can paradoxically worsen it when administered during traumatic stress. These findings highlight that glutamate-based treatments are not universally protective and must be understood in the context of prior stress history.
By defining how early life stress reshapes glutamate signaling and synaptic plasticity, this work aims to clarify why certain interventions succeed or fail. Ultimately, it seeks to inform safer, more precise strategies for preventing or reversing the long-term behavioral consequences of early trauma.