Structural and Functional Development of Inhibitory Connections from the Medial Nucleus of the Trapezoid Body to the Superior Paraolivary Nucleus.

The medial nucleus of the trapezoid body (MNTB) in the auditory brainstem is the principal source of synaptic inhibition to several functionally distinct auditory nuclei. Prominent projections of individual MNTB neurons comprise the major binaural nuclei that are involved in the early processing stages of sound localization as well as the superior paraolivary nucleus (SPON), which contains monaural neurons that extract rapid changes in sound intensity to detect sound gaps and rhythmic oscillations that commonly occur in animal calls and human speech. While the processes that guide the development and refinement of MNTB axon collaterals to the binaural nuclei have become increasingly understood, little is known about the development of MNTB collaterals to the monaural SPON. In this study, we investigated the development of MNTB-SPON connections in mice of both sexes from shortly after birth to three weeks of age, which encompasses the time before and after hearing onset. Individual axon reconstructions and electrophysiological analysis of MNTB-SPON connectivity demonstrate a dramatic increase in the number of MNTB axonal boutons in the SPON before hearing onset. However, this proliferation was not accompanied by changes in the strength of MNTB-SPON connections or by changes in the structural or functional topographic precision. However, following hearing onset, the spread of single-axon boutons along the tonotopic axis increased, indicating an unexpected decrease in the tonotopic precision of the MNTB-SPON pathway. These results provide new insight into the development and organization of inhibition to SPON neurons and the regulation of developmental plasticity in diverging inhibitory pathways.