Remodelling at the calyx of Held-MNTB synapse in mice developing with unilateral conductive hearing loss.

Structure and function of central synapses are profoundly influenced by experience during developmental sensitive periods. Sensory synapses, which are the indispensable interface for the developing brain to interact with its environment, are particularly plastic. In the auditory system, moderate forms of unilateral hearing loss during development are prevalent but the pre- and postsynaptic modifications that occur when hearing symmetry is perturbed are not well understood. We investigated this issue by performing experiments at the large calyx of Held synapse. Principal neurons of the medial nucleus of the trapezoid body (MNTB) are innervated by calyx of Held terminals that originate from the axons of globular bushy cells located in the contralateral ventral cochlear nucleus. We compared populations of synapses in the same animal that were either sound deprived (SD) or sound experienced (SE) after unilateral conductive hearing loss (CHL). Middle ear ossicles were removed 1 week prior to hearing onset (approx. postnatal day (P) 12) and morphological and electrophysiological approaches were applied to auditory brainstem slices taken from these mice at P17-19. Calyces in the SD and SE MNTB acquired their mature digitated morphology but these were structurally more complex than those in normal hearing mice. This was accompanied by bilateral decreases in initial EPSC amplitude and synaptic conductance despite the CHL being unilateral. During high-frequency stimulation, some SD synapses displayed short-term depression whereas others displayed short-term facilitation followed by slow depression similar to the heterogeneities observed in normal hearing mice. However SE synapses predominantly displayed short-term facilitation followed by slow depression which could be explained in part by the decrease in release probability. Furthermore, the excitability of principal cells in the SD MNTB had increased significantly. Despite these unilateral changes in short-term plasticity and excitability, heterogeneities in the spiking fidelity among the population of both SD and SE synapses showed similar continuums to those in normal hearing mice. Our study suggests that preservations in the heterogeneity in spiking fidelity via synaptic remodelling ensures symmetric functional stability which is probably important for retaining the capability to maximally code sound localization cues despite moderate asymmetries in hearing experience.

Strain-specific differences in the development of neuronal excitability in the mouse ventral nucleus of the trapezoid body.

This investigation compared the development of neuronal excitability in the ventral nucleus of the trapezoid body (VNTB) between two strains of mice with differing progression rates for age-related hearing loss. In contrast to CBA/Ca (CBA) mice, the C57BL/6J (C57) strain are subject to hearing loss from a younger age and are more prone to damage from sound over-exposure. Higher firing rates in the medial olivocochlear system (MOC) are associated with protection from loud sounds and these cells are located in the VNTB. We postulated that reduced neuronal firing of the MOC in C57 mice could contribute to hearing loss in this strain by reducing efferent protection. Whole cell patch clamp was used to compare the electrical properties of VNTB neurons from the two strains initially in two age groups: before and after hearing onset at âˆ¼ P9 and ∼P16, respectively. Prior to hearing onset VNTB neurons electrophysiological properties were identical in both strains, but started to diverge after hearing onset. One week after hearing onset VNTB neurons of C57 mice had larger amplitude action potentials but in contrast to CBA mice, their waveform failed to accelerate with increasing age, consistent with the faster inactivation of voltage-gated potassium currents in C57 VNTB neurons. The lower frequency action potential firing of C57 VNTB neurons at P16 was maintained to P28, indicating that this change was not a developmental delay. We conclude that C57 VNTB neurons fire at lower frequencies than in the CBA strain, supporting the hypothesis that reduced MOC firing could contribute to the greater hearing loss of the C57 strain.