Elisabeth Glowatzki Ph.D
Associate Professor Department of Otolaryngology Head and Neck Surgeryeglowat2@jhmi.edu
Telephone Number: 410-502-7008
Fax Number: 410-614-4748
Department of Otolaryngology Head and Neck Surgery
The Center for Hearing and Balance
720 Rutland Ave.
Baltimore MD 21205
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 mechanisms 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. We study pre-/ and postsynaptic mechanisms that determine auditory nerve fiber properties. This approach hopefully will help us to study general principles of synaptic transmission and specifically to identify the molecular substrates for inherited auditory neuropathies, and other cochlear dysfunctions.
Selected 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, Nature Neuroscience, 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. We find a linear calcium dependence of release in the physiological range of IHC membrane potentials. This is different compared to most CNS synapses where release depends on calcium in a highly nonlinear fashion (Goutman and Glowatzki, PNAS, 2007). Interestingly, IHCs may have a different calcium sensor compared to CNS synapses and further characterization of this unknown sensor will help understanding the mechanisms of release at the hair cell synapse.
The outer hair cells (OHCs) in the cochlea help amplifying the sound signal in the periphery. About 5 % of all afferent fibers contact the OHCs, however, up until now, their role has been a complete mystery. Recently, we have been able to record from these fibers in excised cochleae and have provided an initial characterization of their properties. Synapses between OHCs and afferents are also mediated by AMPA receptors, however, do not operate by multivesicular release. Synaptic currents are small, and most likely summation of synaptic currents in response to high intensity sound signals is necessary to activate these fibers (Weisz et al., Nature 2009). The question remains what the function of these fibers is. Are they reporting damaging sound levels? These question will be further investigated.