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Modulation and intrinsic factors influencing spike reliability and precision in the auditory system

Posted on:2017-12-22Degree:Ph.DType:Dissertation
University:State University of New York at BuffaloCandidate:Yang, YangFull Text:PDF
GTID:1454390008490934Subject:Neurosciences
Abstract/Summary:
Neurons in the auditory pathway fire spikes with high fidelity and precision. This feature is very important for temporal information processing and sound localization. Therefore mechanisms dedicated to preserving and improving fidelity in spiking are of central importance to sound processing. To understand such mechanisms, I focused on the synapse formed by auditory nerve fibers (ANFs) onto bushy cells (BCs) in the anteroventral cochlear nucleus (AVCN). This auditory nerve synapse plays a crucial role by conveying temporal information from ANFs to higher auditory centers in the auditory pathway.;One factor that contributes to fidelity is modulation. Modulation influences processing of sound information, especially at early stages of the auditory pathway, which has large consequences for downstream auditory centers, and thereby hearing. Modulation can occur by both targeted neurotransmitter release acting at synaptic or perisynaptic receptors and by changes in ambient neurotransmitter levels that act at extrasynaptic receptors. I focused on the physiological role of ambient glutamate using voltage-clamp and current-clamp experiments. I found that ambient glutamate plays a significant role in modulating BC excitability and enhancing the spike probability, through tonic activation of extrasynaptic NMDA receptors (NMDARs) and metabotropic glutamate receptors (mGluRs). I also found that the fidelity of spiking could be modulated through changing ambient glutamate level. This modulation provides considerable flexibility in the functional state of this synapse (Chapter 2)..;Another major factor that regulates fidelity is how postsynaptic spikes are initiated, which depends critically on the properties of sodium channels. These channels are crucial for triggering the spike itself, so their properties are important to understand. Remarkably, BCs have non-overshooting spikes with minimal contribution from the somatic compartment. In addition, other auditory neurons which encode precise temporal information also lack somatic spikes. However, the reason for this unusual intrinsic property is unclear. I studied the functional effects of somatic sodium conductance (g Na) in BCs using a new, fast dynamic-clamp system. The properties of the dynamic-clamp interface are set out in Chapter 3. I used this dynamic clamp to add gNa to the soma, which yielded normal, overshooting spikes. However, increasing gNa also had major negative consequences. With increasing gNa, the spike probability decreased during evoked synaptic activity. In addition, gNa also degraded the precision of coincidence detection. Thus, low somatic gNa appears to be an adaptation for enhancing fidelity and temporal precision in BCs (Chapter 4)..
Keywords/Search Tags:Auditory, Precision, Fidelity, Spike, Temporal, Modulation, Gna, Bcs
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