Elisabeth Glowatzki, Research Description


    Synaptic Transmission in the Inner Ear 


       Auditory synapses are specialized for fast and precise neurotransmission.  To execute demanding tasks such as directional hearing, we can detect timing differences between both ears as small as only tens of microseconds.  The first, crucial, synapse in the auditory pathway translates the inner hair cell (IHC) receptor potential into trains of action potentials (APs) in auditory nerve fibers.  The functional capacities of this synapse critically determine how sound is coded and transmitted to the brain.  However, investigation of cellular mechanism of synaptic transmission at this synapse has been limited due to its inaccessibility.  We are using dendritic patch clamp recordings to examine mechanisms of synaptic transmission at this first, critical synapse in the auditory pathway.  With this technique we can diagnose the molecular mechanisms of transmitter release at uniquely high resolution (this is the sole input to each afferent neuron), and relate them directly to the rich knowledge base of auditory signaling by single afferent neurons.  This approach hopefully will help us to identify the molecular substrates for inherited auditory neuropathies, and other cochlear dysfunctions.


 Recent Studies


            Characterizing afferent synaptic currents in auditory nerve fibers, we found glutamate (AMPA) receptor mediated excitatory postsynaptic currents (EPSCs). Interestingly, we found that this specialized ribbon-type synapse, vesicles are not released in a one by one fashion, but in coordinated groups (multivesicular release), resulting in EPSCs with varying amplitudes (from 20-800 pA) at single ribbon synapses (Glowatzki and Fuchs, 2002).

Using simultaneous recordings from IHCs and afferent auditory nerve fibers we have characterized the voltage and calcium dependence of release at the IHC afferent synapse (Goutman and Glowatzki, 2007). We find a linear calcium dependence of release in the physiological range of IHC membrane potentials. This relation assures that sound intensity can be coded at this synapse linearly, without any distortion. It has been suggested for a long time, that adaptation in the auditory nerve in response to sound might be due to depression at the IHC afferent synapse as the IHC. The reasoning is that the receptor potential does not adapt in response to sound, however postsynaptically, the auditory nerve fiber activity does adapt. With simultaneous recordings we have now shown directly that synaptic depression occurs at the IHC afferent synapse in response to a constant IHC depolarization. This depression persists after postsynaptic receptor desensitization is removed and therefore we conclude that a presynaptic mechanism like exhaustion of vesicles ready for release must be causing synaptic depression (Goutman and Glowatzki, 2007).

Together with Dwight Bergles laboratory at Johns Hopkins we study the impact of supporting cells on afferent synaptic transmission in the cochlea. In supporting cells directly surrounding the IHCs we have characterized glutamate transporter currents (Glowatzki et al. 2006). These transporters are mediating the uptake of glutamate released from hair cells. Excess glutamate in the extracellular space can cause excitotoxicity and damage afferent terminals as has been shown by Hakuba et al., 2000 (J Neurosci,  20(23):8750-3). Therefore glutamate transporter activity is important for preventing hearing loss.


Current Members of the Laboratory


Lisa Grant, Ph.D.

Isabelle Roux, Ph.D.

Eunyoung Yi, Ph.D.


Former Members of the Laboratory 


Juan Goutman, Ph.D.

Sonja Pyott, Ph.D.