Development and Plasticity of Synaptic Function in the Rodent Auditory Brainstem

Of the five main human senses, hearing is particularly specialized in processing neural signals with a temporal precision significantly higher than reported for the rest of the central nervous system (CNS). The medial nucleus of the trapezoid body (MNTB), with its main synapse, the calyx of Held synapse, has a preeminent role in sound localization. Due to its unusual size and good accessibility for direct electrophysiological investigations, the calyx became a widely used model for the study of short term plasticity (STP). However, the developmental regulation of short term facilitation (STF) and depression (STD) and their contribution to transmission reliability in vivo was still debated. After summarizing the current knowledge concerning the development of the pre- and postsynaptic terminals at the main synapse of the MNTB in Chapter 2, this thesis presents technical advances allowing the reliable study of electrophysiological properties of the calyx in vivo and in vitro across postnatal development. In Chapter 3 we investigate the electrophysiological properties contributing to postsynaptic responsiveness of the principal cell of the MNTB, starting immediately after birth. Here we show that principal cells can fire action potentials in response to synaptic potentials no larger than a few quanta and consequently, in the first postnatal days, synapse formation and maturation may be supported by spontaneous release alone. To investigate the contribution of STD and STF to firing reliability in vivo, in Chapter 4, we validate the feasibility of applying loose patch juxtacellular recordings to measuring the electrophysiological properties of the calyx of Held. The application of this technique in vivo reveals that the young adult calyx is a reliable synapse, where the sizes of electric postsynaptic potentials is independent of firing frequency due to a lower extracellular calcium concentration, compared to standard slice conditions, and a partial chronic depression induced by spontaneous activity. Chapter 5 investigates the contribution of STP to neuronal transmission and its developmental regulation at the calyx of Held synapse. The pronounced STP observed at the young synapse decreased dramatically such that the calyx is prepared for its function as a relay synapse already before hearing onset. Finally, Chapter 6 examines the possible modulation of release probability by GABA, the main inhibitory neurotransmitter in the CNS, via presynaptic GABAB receptors at the calyx of Held. Here, our results suggest a secondary role for GABA at the adult MNTB and show that spontaneous activity has a higher impact on STD.

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