In the developing nervous system, billions of neurons form intricate networks that detect, transmit and process different types of information, such as vision, movement, and memory. These diverse circuits are assembled using a relatively small number of molecules that mediate a common series of events, from cell fate determination and axon guidance to synapse formation and activity-dependent refinement. How then do individual circuits acquire their specialized features? We use molecular and genetic tools in the mouse to tackle this question. Much of our work focuses on auditory circuits, where we can link changes in circuit organization to circuit function and animal behavior, with direct implications for human hearing loss. In addition, we study how versatility at the molecular level allows broadly active signaling systems to elicit distinct effects in different contexts, work that is currently focused on the retina and spinal cord where we can easily distinguish and measure effects on neuronal morphology, synapse localization, and axon trajectory.
Because our ultimate goal is to understand how circuits acquire their functional properties, we place emphasis on the use of mouse models that allow us to isolate, visualize, and alter specific features of the circuit and then study the consequences for circuit activity and perception. Thus, projects rely on a wide repertoire of tools, including single cell RNA-sequencing, CRISPR/cas-9 mutagenesis, viral delivery, time lapse imaging, and electrophysiology. While many methods are in routine use in the lab, we are also involved in a number of collaborations that allow us to pursue each research question with greater depth and rigor.
Because our ultimate goal is to understand how circuits acquire their functional properties, we place emphasis on the use of mouse models that allow us to isolate, visualize, and alter specific features of the circuit and then study the consequences for circuit activity and perception. Thus, projects rely on a wide repertoire of tools, including single cell RNA-sequencing, CRISPR/cas-9 mutagenesis, viral delivery, time lapse imaging, and electrophysiology. While many methods are in routine use in the lab, we are also involved in a number of collaborations that allow us to pursue each research question with greater depth and rigor.
Assembly and Maintenance of Auditory CircuitsWe study the emergence of circuit specializations in the auditory system, where individual neurons exhibit stereotyped differences in projection patterns, synaptic connectivity, and firing properties that are essential for an animal’s ability to perceive sound. In addition, we study how these features are maintained, in hopes of finding ways to protect or repair auditory circuits from noise-induced damage and aging. We use interdisciplinary approaches to investigate several aspects of auditory circuit development, function, and maintenance:
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Molecular VersatilityA second goal is to learn how individual molecules elicit distinct outcomes in different cellular contexts, an important mechanism for creating circuits with particular patterns and properties. Towards this end, we are studying how a single large atypical cadherin, Fat3, ensures that retinal amacrine cells and their dendrites are properly positioned and oriented in order to mediate the polarized flow of information from photoreceptors to retinal ganglion cells. In addition, we continue to investigate the versatile properties of the canonical axon guidance molecule Netrin-1, which acts both permissively and instructively, even in the same neurons.
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