Cognition, perception, and behavior all rely on the activity of precisely organized networks of neurons. We have a strong understanding of the basic developmental mechanisms that guide circuit assembly, from cell fate determination to axon guidance to synapse formation and refinement. But how are these relative generic events coordinated to create the highly specialized neural circuits that allow us to see, hear, think, and react? We study this question in two complementary sensory systems: the ear and the eye. In the auditory system, a relatively homogeneous population of sensory ganglion neurons faithfully transmits sound information from hair cells in the cochlea to target neurons in the auditory brainstem. We are analyzing the transcriptional networks that ensure that these neurons acquire the characteristics required for the perception of sound, with the long term goal of recreating these events in stem cells. We have also begun to further dissect the auditory neuron population to identify additional subtypes that contribute to auditory function and map their patterns of connections. In parallel, we are studying how another type of neurons, the amacrine cells of the retina, develop their own unique features and how these properties impact the wiring of the eye. Remarkably, we have found that even subtle changes in amacrine cell morphology can induce a major rearrangement of retinal circuits.

We employ a wide variety of techniques to analyze the molecular properties of individual proteins and then link these properties back to the whole animal. We define transcriptional networks using RNA-seq and ChiP assays and dissect signaling pathways using biochemical approaches such as yeast two hybrid screens and mass spectrometry. Although most studies rely on generation and analysis of transgenic mice, additional insights into mechanism are gained using in vitro assays and electroporations. We have also begun to apply cutting edge single cell RNA-seq methods to identify new subtypes of neurons. Taking advantage of the growing repertoire of tools for studying the mouse nervous system, we are able to visualize and manipulate neural networks, including live imaging of neurons in situ. Since defects in hearing are easily detected using behavioral and electrophysiological assays, we are ultimately able to correlate cellular defects with changes in auditory function.