Lucas Martin Cheadle

The powerful influence of sensory experience on brain development has been appreciated since the 1960s. Yet, even today, the fundamental cellular and molecular mechanisms through which sensory input shapes developing neural circuits remain largely mysterious. The Cheadle lab recently discovered that sensory experience alters gene and protein expression in microglia, the resident immune cells of the brain. These sensory-induced changes allow microglia to interact with neighboring neurons to strengthen and maintain a subset of synaptic connections and to eliminate others. These findings raise the exciting possibility that microglia, which are predominantly associated with immune responses to injury and disease, also decode salient features of the physical world and contribute to neural responses to the environment.

The Cheadle lab applies a multidisciplinary approach to the visual system of the mouse to investigate the contributions of microglia to sensory experience-dependent synapse development and plasticity. They further seek to identify the molecular mechanisms through which microglia effect changes at synapses and thereby exert control over brain function. To accomplish this, the Cheadle lab images microglial interactions with synapses in the brains of living mice, which allows the researchers to characterize the specific features of the environment to which microglia respond. In parallel, the research team uses cutting-edge single-cell transcriptomic and genomic strategies, such as single-cell RNA-sequencing, to profile the molecular changes in microglia that are elicited by distinct sensory stimuli. With these combined approaches, the Cheadle lab is interrogating the ways in which environmental stimuli converge upon the microglial genome to shape neural circuit development and function.