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.
