This proposal focuses on investigating the mechanism of synaptic transmission at the inner hair cell (IHC) afferent synapse in the mammalian cochlea. This most peripheral chemical synapse in the auditory pathway serves as an interpreter translating the hair cell receptor potential into a train of excitatory postsynaptic potentials that activate action potentials in the afferent auditory nerve fibers. The specific features of the IHC afferent synapse critically determine how a sound signal is coded in the inner ear and transmitted to the brain via auditory nerve fiber activity.
Our aim i s to characterize pre- and postsynaptic mechanism that shape the postsynaptic activity in IHC afferent fibers. We will record postsynaptic activity using the whole cell patch clamp method. The recording sites will be the afferent fiber terminal directly at the inner hair cell synapse and the afferent fiber soma in the spiral ganglion in excised preparations of rat and mouse cochleae. To exactly describe the relationship between presynaptic stimulus and postsynaptic activity, we will make double recordings from IHCs and afferent fiber terminals. To affect transmitter release and define the quantal size, we will record excitatory postsynaptic currents and vary experimental conditions; i.e. changing the temperature or ionic environment and using release-affecting toxins. To understand postsynaptic determinants of synaptic transmission, we will provide a basic description of the waveform of the excitatory postsynaptic potential and its relation to the activation of action potentials. Using pharmacological tools, we will try to identify individual components that shape the postsynaptic potential waveform starting with a focus on different classes of potassium channels. We will also study the role of efferent inputs onto afferent fiber activity. Most recordings will be performed in the already established preparation using postnatal cochleae. In parallel we will extend our recordings to mature cochleae, as our ultimate aim is to understand both development and adult function of the IHC afferent synapse. These studies will further our knowledge of basic mechanisms of peripheral hearing and therefore also will lead to a better understanding of abnormal hearing and deafness.
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