Picower Plastic Lunch with the Tsai Lab

Speaker: Mat Victor, PhD

Zoom Link: https://mit.zoom.us/j/93861145558 (MIT credentials are required)

Talk Title: Modeling the Impact of Microglial States on Neuronal Network Dynamics

Abstract: In addition to actively scavenging the brain parenchyma for signs of pathogens, microglia can monitor neuronal activity, eliminate and remodel neuronal synapses, and support myelin turnover. Although the cellular mechanisms by which microglia sense dysfunctional network activity are still poorly understood, it has been speculated that neurological diseases that are typified by altered neuronal excitability may partly manifest through early deficits in microglial surveillance and regulation of neuronal networks. Nevertheless, the study of neuron-microglia communication in the context of human pathobiology has been hindered by extensive species-specific differences between human and rodent microglia. Microglia-like cells derived from human induced pluripotent stem cells (iPSCs) are a promising new model system to dissect the causal role of microglia in disease-associated network-level deficits. However, it remains unclear to what extent these cells may be employed for such studies. Here I’ll discuss our ongoing effort to model the functional repertoire of altered microglial states and its impact on the architecture and activity of neuronal networks. To do so, we are employing state-of-the-art cellular reprogramming technologies to derive three-dimensional brain cell cultures from Alzheimer’s disease (AD) patient-derived stem cells in combination with a variety of system-level tools to observe and drive neural activity. Our goal is to empirically validate and functionally interrogate the role of microglia in driving AD progression at the network-level, and to identify interventions aimed at relieving neuronal circuit dysfunction.