Ultrastructural Analysis of Excitatory and Inhibitory Synapses within the Medial Nucleus of the Trapezoid Body of Normal Hearing and Congenitally Deaf Mice

The auditory brainstem has been the area of much focus in recent years due to its advantages in circuitry and synaptic connections. The endbulbs and calyces of Held are large, glutamatergic synapses within the AVCN and MNTB, respectively. Because of their large size and accessibility these synapses have offered the ability to study pre- and post-synaptic mechanisms of neurotransmission within the central nervous system. The calyx of Held synapse is the main excitatory input into the MNTB principal cells, containing hundreds of individual synaptic specializations, or release sites. Previous studies have identified physiological and morphological changes at the endbulb of Held synapse but not the calyx of Held synapse. However, changes in inhibitory innervation at the MNTB were observed as a result of altered input. In this study we have utilized the calyx of Held synapse, apposing inhibitory terminals within the MNTB of CBA/J and congenitally deaf mice (dn/dn) to examine the role of altered input on synaptic strength. The dn/dn strain is of particular importance because they exhibit no spontaneous activity within the VIIIth nerve fiber, lending itself as a valuable model in the altered input studies, particularly an absence of afferent input. Serial electron microscopic analysis of the fine structure of the calyx of Held and inhibitory contacts onto the MNTB principal cells were compared between normal and deaf. Strikingly, the calyceal active zones within the adult deaf animals were significantly larger compared with normal hearing animals despite the fact there were no changes in excitatory currents. Examination of the inhibitory terminals confirmed the increase in mIPSC frequency manifested in an increase in inhibitory synapses expressed on the MNTB principal cells