Traumatic Stress Recruits an Excitatory Orbitofrontal-Amygdala Pathway to Drive Maladaptive Aggression

Author

• Mikaela Aholt, Southern Illinois University CarbondaleFollow

Date of Award

5-1-2026

Degree Name

Master of Science

Department

Molecular Cellular and Systemic Physiology

First Advisor

Nordman, Jacob

Abstract

Traumatic stress is a reliable predictor of heightened aggression, yet the mechanisms linking stress exposure to aggression remain poorly understood. The Nordman lab previously found that traumatic stress activates the posterior ventral segment of the medial amygdala (MeApv) to drive persistent increases in aggressive behavior. However, why traumatic stress would engage an aggression-promoting pathway is unclear. To address this, the inputs to the MeApv were mapped and a population of excitatory, but not inhibitory, neurons in layer 5 of the medial orbitofrontal cortex (mOFC) were identified. The OFC is classically viewed as an inhibitory brake on amygdala-driven impulses, yet emerging evidence suggests it can also facilitate context-dependent emotional responses. Notably, traumatic stress is known to disrupt OFC function and its connectivity with the amygdala, implicating this circuit in pathological aggression. Using fiber photometry, I showed that traumatic stress selectively activates these MeApv-projecting excitatory mOFC neurons as well as their downstream MeApv outputs. Chemogenetic inhibition of these excitatory mOFC neurons during traumatic stress exposure prevented the subsequent increase in aggression while preserving non-aggressive social behavior. This work establishes a causal link between OFC dysfunction and aggression following traumatic stress and highlights the mOFC–MeApv pathway as a potential target for therapeutic intervention in stress-related aggression disorders.