Remodelling at the calyx of Held–MNTB synapse in mice developing with unilateral conductive hearing loss
Authors: Grande Giovanbattista , Negandhi Jaina , Harrison Robert V. , Wang Lu‐Yang 
Published: January 2014

Key points
Severe forms of hearing loss during development are well known to profoundly alter synaptic structure and function through the auditory neuraxis; however, the pre‐ and postsynaptic modifications that occur during development following moderate forms of unilateral hearing loss remain unknown.
We performed anatomical and electrophysiological experiments at the calyx of Held synapse in slices taken from mature mice developing with a unilateral conductive hearing loss and compared populations of synapses in the same animal that were either sound deprived or sound experienced.
Compared to normal hearing mice, we found that calyx of Held synapses that were both sound deprived and sound experienced as a result of a unilateral conductive hearing loss were (1) structurally more complex, (2) had smaller synaptic currents and a readily releasable pool size, and (3) were more excitable.
Despite these changes in structure and function, spiking fidelity within the populations maintained a continuum as in normal hearing mice such that heterogeneities remained bilaterally symmetric.
Preservations in the heterogeneity in spiking fidelity via synaptic remodelling may ensure that a functional stability important for the ability to code sound localization cues is maintained despite asymmetries in hearing experience during development.
AbstractStructure 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.