Figure 2. Hearing loss affects development of medial nucleus of the trapezoid body inhibitory afferents to brainstem nuclei.

(A) (Top) Simplified schematic of a gerbil receiving two important sound cues for localization, ILD and ITD. (Bottom) Slice preparations showing the neural circuits that process these cues. ILD coding in the LSO nucleus is represented by the integration of excitatory drive from sound at the ipsilateral ear and MNTB inhibitory input driven by sound at the contralateral ear. ITD coding in the MSO nucleus is represented by the coincidental timing of excitatory drive from the two ears. MNTB inhibitory inputs to the MSO are involved in fine-tuning the ITD sensitivity of MSO neurons. (B) Hearing loss prevents the developmental refinement of inhibitory projections to the LSO and MSO. (Left) In the control LSO, inhibitory arborizations are spatially restricted along the frequency axis. The branching pattern of a single MNTB axon is shown within the LSO. Following contralateral SNHL, these arbors are significantly expanded, suggesting perturbed specificity [53]. (Right) In the control MSO, inhibitory projections are restricted to the soma. A schematic is shown of a single MSO neuron receiving MNTB inhibitory input with the red circles representing terminal boutons. Following contralateral SNHL, the inhibitory synapses remain distributed across the somatodendritic axis, and do not become localized to the soma [56].

ILD: Interaural level difference; ITD: Interaural time difference; LSO: Lateral superior olivary; MSO: Medial superior olivary; SNHL: Sensorineural hearing loss.