The calyx of Held synapse is a key element in the circuitry that supposedly computes sound source localization in the mammalian auditory brain stem. Precise timing of action potential output from this synapse is central for this task but the mechanisms that modulate and preserve output is not well understood. During repetitive afferent fiber stimulation, this synapse suffers robust synaptic depression which limits its ability to sustain prolonged output of discharges. The first hypothesis to be tested is that vesicle pool depletion is the main factor behind this short-term form of plasticity. The large size of the calyx terminal allows one to simultaneously patch clamp a single calyx terminal and the postsynaptic cell, and thus, to measure presynaptic calcium currents and evoked EPSCs. Presently, this synapse is the only site in the brain where pre- and postsynaptic recordings can be made simultaneously. Voltage clamp protocols designed to elicit maximal presynaptic Ca influx will be used to fully deplete the releasable pool of vesicles, and to determine its size and recovery rate. The limit on action potential output, set by vesicle pool depletion, will thus be determined quantitatively. The second hypothesis is that glutamate transporters are critical for the synapse to maintain spikes at high frequencies. The function and locus of glutamate transporters at this synapse are unknown. To determine their function, the proposed work will examine first the effect of different transporter antagonists on presynaptic Ca currents and EPSCs. The PI plans to determine if transporters prevent glutamate """"""""spillover"""""""" from the synaptic cleft, which in turn prevents the activation of mGluRs that inhibit Ca currents and EPSCs. Recordings of transporter mediated currents in the calyx, MNTB cell, or surrounding glia will then determine the locus of transporters and the time course of glutamate clearance. The third hypothesis is that activation of the numerous inhibitory bouton inputs onto MNTB neurons significantly alters membrane excitability, and thus, the spike output of the cell. By independently activating the bouton IPSCs and the calyceal EPSCs, they plan to determine how the interaction between excitatory and inhibitory inputs affects spike timing. The unique features of the synapse allow a systematic study of the underlying mechanisms that control spikes and may provide new insight into how synaptic properties adapt to preserve the timing of information flow through auditory pathways.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
1R01DC004274-01
Application #
6027630
Study Section
Special Emphasis Panel (ZRG1-IFCN-6 (01))
Program Officer
Luethke, Lynn E
Project Start
2000-03-01
Project End
2005-10-31
Budget Start
2000-03-01
Budget End
2001-02-28
Support Year
1
Fiscal Year
2000
Total Cost
$197,041
Indirect Cost
Name
Oregon Health and Science University
Department
Neurosciences
Type
Schools of Medicine
DUNS #
009584210
City
Portland
State
OR
Country
United States
Zip Code
97239
Johnson, Stuart L; Olt, Jennifer; Cho, Soyoun et al. (2017) The Coupling between Ca2+ Channels and the Exocytotic Ca2+ Sensor at Hair Cell Ribbon Synapses Varies Tonotopically along the Mature Cochlea. J Neurosci 37:2471-2484
Sebe, Joy Y; Cho, Soyoun; Sheets, Lavinia et al. (2017) Ca2+-Permeable AMPARs Mediate Glutamatergic Transmission and Excitotoxic Damage at the Hair Cell Ribbon Synapse. J Neurosci 37:6162-6175
Rudolph, Stephanie; Tsai, Ming-Chi; von Gersdorff, Henrique et al. (2015) The ubiquitous nature of multivesicular release. Trends Neurosci 38:428-38
Cho, Soyoun; von Gersdorff, Henrique (2014) Proton-mediated block of Ca2+ channels during multivesicular release regulates short-term plasticity at an auditory hair cell synapse. J Neurosci 34:15877-87
Li, Geng-Lin; Cho, Soyoun; von Gersdorff, Henrique (2014) Phase-locking precision is enhanced by multiquantal release at an auditory hair cell ribbon synapse. Neuron 83:1404-17
Kim, Mean-Hwan; Li, Geng-Lin; von Gersdorff, Henrique (2013) Single Ca2+ channels and exocytosis at sensory synapses. J Physiol 591:3167-78
Kim, Jun Hee; von Gersdorff, Henrique (2012) Suppression of spikes during posttetanic hyperpolarization in auditory neurons: the role of temperature, I(h) currents, and the Na(+)-K(+)-ATPase pump. J Neurophysiol 108:1924-32
Cho, Soyoun; von Gersdorff, Henrique (2012) Ca(2+) influx and neurotransmitter release at ribbon synapses. Cell Calcium 52:208-16
Graydon, Cole W; Cho, Soyoun; Li, Geng-Lin et al. (2011) Sharp Ca²? nanodomains beneath the ribbon promote highly synchronous multivesicular release at hair cell synapses. J Neurosci 31:16637-50
Cho, Soyoun; Li, Geng-Lin; von Gersdorff, Henrique (2011) Recovery from short-term depression and facilitation is ultrafast and Ca2+ dependent at auditory hair cell synapses. J Neurosci 31:5682-92

Showing the most recent 10 out of 17 publications