Projects in the lab concern the properties of auditory nerve fiber synapses (called “endbulbs of Held”), and how they influence hearing. There are several themes:
Endbulbs and bushy cells change their properties in the presence of modulatory substances, including the neurotransmitters glutamate and GABA. We are interested in how these modulators regulate the efficacy of the synapse, as well as how they are themselves regulated.
Endbulbs change with use through a number of mechanisms, including vesicle depletion and delayed release. These mechanisms are active on the time-scale of a few seconds, so are called short-term plasticity. We study how these forms of plasticity influence the relaying of activity from the auditory nerve to bushy cells, and how this could contribute to normal hearing.
Endbulb short-term plasticity. Traces show synaptic currents (left) and spiking (right) in bushy cells during auditory nerve stimulation at 100 Hz (blue) or 333 Hz (red). Depression of synaptic currents is matched by decreased spiking.
Activation of modulatory GABA receptors reduces spiking (red trace). Activation of modulatory glutamate receptors restores spiking (blue trace). From Chanda & Xu-Friedman (2011).
We recently discovered that auditory nerve synapses are affected by abnormal sound levels. Both long-term noise exposure and plugging of the ears trigger changes in bushy cells and endbulbs that may support hearing in the new acoustic conditions. This has important implications for people exposed to loud environments for prolonged periods, such as during work or travel, or for children who suffer from ear infections. We are studying the mechanisms underlying these changes, how these changes may support normal hearing, as well as how they could underlie problems that outlast the abnormal acoustic conditions.
Acoustic experience changes endbulbs. Exposure to noise reduces depression (red trace), while plugging the ear increases depression (blue trace). There are also changes in synaptic structure and bushy cell spiking.
In vivo responses
We have begun using in vivo experiments to learn the functional effects of synaptic properties. We have been studying how prolonged exposure to loud, but non-traumatic noise affects auditory nerve and bushy cell responses.
Tools for studying synaptic physiology
We have developed software to assist us in collecting and analyzing electrophysiology data, which are freely available under the mafPC link.