2025 Seed Grant
Jessica L. Bolton, Ph.D.
Georgia State University
All humans are born with a unique combination of genes, which contribute greatly to who we are. However, early-life experiences such as trauma or hardship, particularly during the first few years of childhood, can also influence our brain long-term. This is important because how our brain develops and is altered by early-life experience helps determine if we will be vulnerable or resilient to neuropsychiatric disorders such as depression and addiction. How do early-life experiences, especially adversity, alter our brain circuits? If we
understand how this occurs, can we prevent it from happening to minimize the vulnerability to neuropsychiatric disorders in at-risk children? —This is the focus of my research project.
Our brain circuits are composed of billions of cells called neurons that communicate through connections called synapses. We find that synapses in stress-sensitive circuits are changed in response to early-life adversity, and these changes predict vulnerability to stress-related disorders like depression later in life. My previous work has identified microglia, the resident immune cells of the brain, as key regulators of these synaptic changes because they play an important role in synaptic pruning during development. Specifically activating microglia with a new, non-invasive chemogenetic (genetically engineered) approach during the traumatic early-life experience is sufficient to prevent the changes in synapses and aberrant stress response behaviors, thus indicating the promise of this approach for developing future therapeutic interventions. However, we do not yet understand how this chemogenetic approach is able to rescue microglial function and prevent the early-life adversity-induced outcomes, which is critical for harnessing its
therapeutic potential. My research employs cutting-edge techniques to decipher the cellular and molecular mechanisms by which early-life adversity disrupts microglial function, and how this is rescued by the microglia-specific chemogenetic intervention. Findings from this project will allow us to develop novel treatments to modify how microglia influence brain circuits—with enormous promise to change human vulnerability to neuropsychiatric disorders.
