The interrogation of auditory activity and molecular genetics on the development of sound localization neurons

The body of work presented here is a series of manuscripts in varying states of publication that represent the work performed by the author. In brief, these works have focused on unraveling on a cellular level how the auditory brain builds a spatial map of one’s environment discretely from sound stimuli which fundamentally lack spatial information. Neurons in the brain region known as the Medial Superior Olive (MSO) integrate differences in the arrival time of sound stimuli between two ears, while neurons in the Lateral Superior Olive (LSO) integrate differences in the intensity of sound stimuli. Cells in both regions use their unique strategies to compute spatial information, split based on the frequency of incoming sound. In the manuscripts presented here (Chapter 4), we demonstrate that neurons in the LSO do not strictly adhere to previous historical dogma (use of predominantly high frequency sounds), and instead show exquisite temporal resolution more like MSO neurons. Specifically, our work demonstrates a neural “vetoing” mechanism in which spatially precise inhibition overrides the integration of somatodendritic excitatory signals due to its localization on the axon initial segment of neurons. For the remaining work (Chapters 3 & 5), we discuss how MSO neurons exhibit a continuum of response properties, ranging from neurons with exquisite temporal precision, to neurons with incredibly slow properties that are poor coincidence detectors. These slow MSO neurons were previously assumed to be non-principal neurons, but throughout this body of work we demonstrate that all MSO neurons are principal neurons that exist along a continuum of firing response properties and all project to downstream auditory centers. Furthermore, we deeply investigate how this continuum of response properties arises: whether through development, auditory activity, or an interdependence. Interestingly, the diversity of MSO response properties arises predominantly through developmental changes to the transcriptome of cells. The spectrum of response properties is almost entirely filled out, and only minorly fine-tuned by auditory activity. Together, this data heavily implies that MSO neurons are fated to become coincidence detectors, but across a much wider range of temporal disparities than previously appreciated.