The trillions of connections between brain cells enable complex thought and behavior. These connections are wired with great precision through both genetics and in response to an organism’s experiences. Our lab seeks to understand how experiences engage specialized immune cells called microglia to shape the connectivity and function of the brain. We are further interested in how impairments in these processes can contribute to neurodevelopmental disorders such as autism.
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.
Cold Spring Harbor Laboratory: Science is hope
December 21, 2020
The Laboratory is a leading research center for genetics, cancer, plant biology, quantitative biology, and neuroscience.
Assistant Professor Cheadle named Next Generation Leader
November 19, 2020
CSHL Assistant Professor Lucas Cheadle has been named a Next Generation Leader by the Allen Institute for Brain Science.
Immune cells sculpt circuits in the brain
September 14, 2020
Immune cells play an unexpected role in fine-tuning the brain’s neural circuits.
How the senses shape the brain
August 6, 2020
Neuroscientist Lucas Cheadle joins CSHL neuroscience faculty, and studies how outside stimuli affect brain development.