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dc.contributor.advisorXu-Friedman, Matthew
dc.contributor.authorZhuang, Xiaowen
dc.date.accessioned2018-10-26T02:55:17Z
dc.date.available2018-10-26T02:55:17Z
dc.date.issued2018
dc.date.submitted2018-08-02 12:37:03
dc.identifier.urihttp://hdl.handle.net/10477/78549
dc.descriptionPh.D.
dc.description.abstractInformation transfer at chemical synapses occurs when vesicles fuse and release neurotransmitter. This process is tightly regulated and must maintain stable function when faced with different levels of activity. Three main factors are involved in determining synaptic strength: the number of vesicles (N), the postsynaptic response to a single synaptic vesicle (Q) and release probability (Pr). However, it is not clear how these properties are regulated at synapses that undergo different levels of activity and what the underlying mechanisms of this regulation are. In order to address the above issues, I focused on auditory nerve synapses, called endbulbs of Held. Endbulbs are made by auditory nerve fibers onto bushy cells (BCs) in the anterior ventral cochlear nucleus. Auditory nerve fibers have a great diversity in firing rate due to their different sound level sensitivity (Liberman, 1978). Moreover, abnormal auditory activity is associated with hearing problems including tinnitus and processing disorders. Therefore, this raises the question how these synaptic properties are regulated. I studied the regulation of endbulbs by exposing mice to different acoustic conditions, using ear-occlusion to reduce auditory activity and noise-rearing to increase auditory activity. I found that after one week of ear-occlusion, endbulbs showed elevated levels of depression compared to normal endbulbs, reflecting higher Pr. I observed no change in Q, and instead there was a compensatory decrease in the number of vesicles N. Both Pr and N showed recovery after returning to normal conditions. Furthermore, bushy cells fired fewer action potentials in response to evoked synaptic activity. I also found that endbulbs older than 50 days showed activity-dependent changes in Pr similar to young endbulbs, suggesting there is no critical period for this phenomenon. Therefore, these results reflect a homeostatic adaptive response of auditory nerve synapses. My results have important implications. They highlight that synaptic properties are tightly regulated through an activity-dependent, homeostatic mechanism. My results also have relevance for reversing long-lasting effects of otitis media (OM) (Chapter 2).Moreover, to understand what the underlying presynaptic mechanisms are and the relative importance of pre- and postsynaptic contributions to spike fidelity, I performed voltage clamp and Ca2+ imaging at endbulbs under noise-rearing and ear-occlusion conditions. I found that the changes in Pr are a result of changes in presynaptic Ca2+ influx. I also used dynamic clamp to distinguish the effects of pre- vs. postsynaptic changes on spike fidelity. Spike fidelity is affected by both presynaptic and postsynaptic adaptations after ear-occlusion and only affected by presynaptic adaptations after noise-rearing. These results are important, because understanding cellular mechanisms will help to treat disorders that result from loud noise exposure or conductive hearing loss. Optimal medications may be designed to reverse synaptic changes that impede normal processing (Chapter 3).
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dc.language.isoen
dc.publisherState University of New York at Buffalo
dc.rightsUsers of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.
dc.subjectNeurosciences
dc.titleActivity-dependent changes at the auditory nerve synapse
dc.typeDissertation
dc.typeText
dc.rights.holderCopyright retained by author.
dc.contributor.departmentBiological Sciences


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