Effects of early life stress on network and behavioral states

• Published in: Psychoneuroendocrinology Vol. 177; p. 107475
• Main Authors: Scarpa, Garrett B., Antonoudiou, Pantelis, Weiss, Grant L., Stone, Bradly T., Maguire, Jamie L.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.07.2025
• Subjects: Amygdala - metabolism; Animals; Basolateral Nuclear Complex - metabolism; Basolateral Nuclear Complex - physiopathology; Behavior; Behavior, Animal - physiology; Disease Models, Animal; Early life stress; Female; Frontal Lobe - metabolism; Frontal Lobe - physiopathology; Interneurons - metabolism; Interneurons - physiology; Male; Maternal Deprivation; Mice; Mice, Inbred C57BL; Networks; Neurons - metabolism; Neurons - physiology; Physiology; Psychiatric vulnerability; Sex differences; Stress, Psychological - metabolism; Stress, Psychological - physiopathology; Networks; Sex differences; Early life stress; Psychiatric vulnerability; Physiology; Behavior
• ISSN: 0306-4530; 1873-3360; 1873-3360
• DOI: 10.1016/j.psyneuen.2025.107475

Adverse childhood experiences (ACEs) are associated with numerous detriments in health, including increased vulnerability to psychiatric illnesses. Early life stress (ELS) in rodents has been shown to effectively model several of the behavioral and endocrine impacts of ACEs and has been utilized to investigate the underlying mechanisms contributing to disease. However, the precise neural mechanisms responsible for mediating the impact of ELS on vulnerability to psychiatric illnesses remain largely unknown. We use behavior, immunoassay, in vivo local field potential (LFP) recording, histology, and patch clamp to describe the effects of ELS on stress-related behaviors, endocrine changes, network states, protein expression, and cellular physiology in male and female mice. We demonstrate that a murine maternal separation (MS) ELS model causes male-specific alterations in behavioral and hormonal responses following an acute stressor. LFP recordings in the basolateral amygdala (BLA) and frontal cortex (FC) reveal similar sex-specific alterations at baseline and in response to acute ethological stress. Furthermore, altered physiology of BLA principal neurons in males and BLA parvalbumin (PV) interneurons in females suggests a likely mechanism through which these effects may be mediated. These findings support a large body of literature demonstrating that these network states contribute to stress reactivity and vulnerability to psychiatric illnesses. Collectively, these results implicate distinct, novel male- and female-specific mechanisms through which ACEs may impact psychiatric health, including altered cellular physiology and network states involved in emotional processing. •Developmental adversity negatively impacts network and behavioral states.•ELS impacts the BLA-FC network and behavior in a sex-specific manner.•ELS induced perturbations in BLA-FC network states may contribute to psychiatric illnesses.•Novel potential mechanism mediating the impact of ELS on behavior.•New perspective on therapeutic interventions for those affected by ACEs.