DEVELOPMENT AND POTENTIAL BEHAVIORAL SIGNIFICANCE OF PRECISE TONOTOPY IN AN INHIBITORY CIRCUIT OF THE AUDITORY BRAINSTEM

Precise neuronal connections are crucial for normal brain function. Often this is accomplished during development, as initially imprecise connections are refined in a manner that depends on neural activity, both spontaneous and sensory-evoked. In the auditory system, many connections are topographically organized according to frequency, or tonotopically, an organizational scheme important for processing information about sound. In this thesis, I investigated the development of precise tonotopy in the inhibitory connections between the medial nucleus of the trapezoid body (MNTB) and the lateral superior olive (LSO), a pathway in the auditory brainstem involved in sound localization. Although MNTB-LSO connections exhibit tonotopy from the outset, tonotopic precision increases during development through a process of silencing imprecise inputs and strengthening maintained connections before hearing onset, followed by anatomical pruning after hearing. I teased apart the relationship between functional and anatomical refinement, as well as the degree to which spontaneous and sound-evoked activity play a role in each. Finally, I attempted to link the tonotopic specificity of this circuit to a specific aspect of auditory perception, frequency discrimination.In Chapter 2, I mapped the tonotopic precision of individual MNTB axons in the LSO over the first three weeks of postnatal development and showed that pruning does not take place before hearing onset, indicating that functional and anatomical refinement take place during distinct developmental periods. In Chapter 3, I showed that anatomical refinement after hearing onset depends on efferent cholinergic transmission in the cochlea, most likely due to its role in patterning pre-hearing spontaneous activity and the functional refinement of connections. In Chapter 4, I showed that eliminating the normal spectrotemporal structure of sound-evoked activity by rearing animals in pulsed white noise does not disrupt pruning. Finally, in Chapter 5, I showed that the loss of tonotopic precision that results from the elimination of cochlear cholinergic transmission is also accompanied by impaired frequency discrimination, providing a link between tonotopic refinement, the efferent system, and auditory perception. I discuss the results in the context of a model of tonotopic refinement and a new role of the efferent system during development