Project Summary The auditory system is an ideal place to study how neurons and circuits develop to encode sensory features with temporal precision. In the cochlear nucleus, specialized cells extract information about the acoustic world and initiate parallel processing pathways, each of which analyzes and encodes continuous auditory cues such as frequency, phase, and amplitude. The octopus cell of the mammalian cochlear nucleus stands out for its unique sensitivity to both the temporal and frequency components of sound stimuli. However, the mechanisms underlying development of tonotopically organized somatic and dendritic synapses in single neurons is not understood. Additionally, there is little understanding of the role of auditory experience in the refinement of morphological and physiological properties that contribute to temporal coding. I propose to carry out an integrated analysis of the molecular and biophysical properties of octopus cells and to track how features develop during the onset of auditory experience. Using the mouse as a model system, I will define the refinement of tonotopically organized inputs to octopus cell somas and dendrites before and after hearing onset while parallel changes in the size and complexity of the dendritic arbor occur. This data will provide insights into the role of auditory experience on the development of brainstem auditory circuits. I will also measure correlated changes in ion channel expression with changes in biophysical properties at developmental timepoints and measure electrophysiological changes as auditory experience first begins. These experiments will bridge the sequence of anatomical refinements with physiological refinements during hearing onset. The research training plan will provide extensive training in developmental neurobiology, methods in mouse molecular genetics, quantitative approaches, and computational image analysis. Training will occur in the rich scientific environment at Harvard Medical School in the Department of Neurobiology. Additionally, the training plan includes continuing education in mentorship, communication, management, diversity, and leadership. The training provided under this plan will provide essential skills for a successful independent research career.

Project Narrative Neurons in the cochlear nucleus are specialized to precisely encode temporal information that is used to localize and interpret auditory information. This proposal will establish how a defined neuronal circuit in the cochlear nucleus develops its mature functional properties. Understanding how projections from the ear interact with neurons in the developing cochlear nucleus will allow for a better understanding of how auditory circuits can become dysfunctional.