The brain is assembled from millions of neurons, which are functionally organized in defined circuits. Each circuit collects, encodes and processes environmental information to trigger a distinct behavioral outcome. Embedded within this network are microglia, a defined population of immune cells. Even though microglia have been known for over 100 years, they have been mostly seen as by-standers in the brain. Only recently, microglia have entered the spotlight in neuroscience because their reactivity not only facilitates refinement of neuronal circuits during brain development, but also destroys those same circuits in neurodegenerative diseases such as Alzheimer’s disease. Whether microglia are simply “by-standers” during adulthood, or whether they actively modulate the adult brain is largely unexplored.
In my talk, I will first establish the fundaments of microglia reactivity. We will show how applying mathematical principles of topology and high dimensional graph representation allows us to correlate microglial reactivity to biologically relevant trajectories from development and disease across multiple brain regions. This strategy brought our attention to ketamine, a recreational drug that is also commonly used for anesthesia. We show that ketamine induces a loss of an extracellular barrier for developmentally locked sensory plasticity, and that microglia are the main mediators of this process. Subsequently, we are proposing a novel strategy to selectively stimulate 60-Hz brain frequency to imitate this effect and to enhance learning in mice. Intriguingly, a gender-specific component is part of the acute effect of ketamine, which we recapitulated in human brain tissue. Finally, I will show how we further dissect the basic molecular and cellular features of microglial function in relation to the nervous system. Overall, our research promotes microglia to an “influencer” of neuronal network function.
Due to COVID this talk will take place online only. A Zoom link will be sent out on the day of the talk through our internal mailing lists - please do not share externally!