Rebecca Lowery, Ph.D. - Postdoctoral Fellow, Dept. Neuroscience, Univ. Rochester
Feb 18, 2021 @ 4:00 p.m.
Microglia, the immune cells of the brain, have a canonical role in regulating neuropathological processes. Recently, they have been implicated as critical mediators of neurophysiological processes such as synaptic plasticity as well. My work has focused on two molecular pathways that allow microglia to communicate with neurons in the context of synaptic plasticity and shown that, rather than functioning as global mediators of plasticity, these signaling mechanisms are utilized in a heterogeneous manner dependent on brain region and developmental period. Disruptions in these pathways can result in behavioral alterations mimicking intellectual and developmental disabilities such as autism spectrum disorders. Given the outcomes of disrupted microglial function, it is important to determine how external stressors such as adverse early life events negatively impact microglial development and subsequent function. Examining the impact of a variety of early life insults, including gestational exposure to environmental contaminants and perinatal alcohol exposure, demonstrated that such insults result in alterations in microglia. These alterations, while subtle, can have significant implications for microglial function and subsequently neuronal circuitry and behavioral outcomes. However, these negative outcomes may be reversible as inducing the turnover of defective microglia into newly-born microglia rescues observed defects in microglial function. These findings provide evidence that microglia may be the element translating negative environmental insults into defects in neuronal wiring underlying a wide variety of neurological disorders and IDDs, and that microglia may be a valid therapeutic target for disorders resulting from synaptic defects.
Host: URMC Dept. Neuroscience