Symposium
Session Room 220
Session Room 220
Tuesday, June 17, 10:50 AM – 12:05 PM
Symposium 7: Susceptibility in the Developing Brain: Why the Timing of Insults and Sex Matter
Early-life exposure to harmful events plays a key role in the development of mental illnesses. A wide range of insults can disrupt the developmental trajectories of specific brain systems, leading to abnormal maturation of particular cell types and states. These changes can result in significant alterations to critical brain circuits, which are linked to the emergence of multiple psychopathological conditions. In this context, animal models serve as invaluable tools for identifying the abnormalities caused by early-life insults, uncovering the underlying mechanisms, and understanding how differential exposures can lead to diverse psychiatric outcomes. A deeper understanding of the relationship between early-life insults, psychiatric disorders, and key neurobiological mechanisms is essential for identifying novel targets for intervention. In this symposium, we will explore factors related to early-life insults and the resulting abnormalities, focusing on the timing of these insults and the sex of the individual. Dr. Marie Eve-Trambley (University of Victoria, Canada) will begin by discussing the role of microglia—the brain’s primary immune cells—during development in health and maternal immune activation. In her presentation, Dr. Tremblay will also introduce "dark microglia," a unique microglial state discovered by her lab in mice and humans. These cells involved in remodeling of the ventral hippocampus are rare in healthy adults but become highly prevalent under chronic stress and disease conditions, including maternal immune activation. Dr. Anthony Grace (University of Pittsburgh, USA) will then dive into the differences in vulnerability between male and female rats. He will show that male rats experience prepubertal vulnerability, driven by the loss of parvalbumin interneurons (PVIs) in the amygdala, while females are more vulnerable after puberty, with stress-induced loss of PV function in the nucleus reticularis-nucleus reuniens pathway. In both cases, the result is a loss of PVIs in the limbic hippocampus and the development of a hyperdopaminergic state. This disruption seems to stem from an early stress-induced premature maturation of the amygdala-prefrontal pathway, which interferes with the normal maturation of the excitation/inhibition balance. Finally, Dr. Felipe Gomes (University of São Paulo, Brazil) will present compelling findings on how adolescent stress increases vulnerability by disrupting immature PV neurons and causing perineuronal net loss in the ventral hippocampus. Interestingly, this vulnerability can be reinstated in adults by breaking down the perineuronal nets before exposure to stress. Together, these presentations will illustrate how early-life insults disrupt multiple brain systems, leading to psychiatric disorders in adulthood. The integration of these findings will guide future research efforts aimed at developing more targeted therapeutic interventions.