Activity-Dependent Changes at the Endbulb of Held
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Synaptic transmission is required for information processing and computation in the brain, which provides a physiological basis for learning and memory. A reliable synaptic transmission depends on three critical factors of neurotransmitter release: the number of vesicles ( N ), the probability of neurotransmitter release ( P r ), and the postsynaptic quantal size ( Q ). However, it is not well understood how a particular synapse regulates NP r Q . To understand the factors involved in regulation of NP r Q , I focused on the auditory nerve (AN) synapse, the endbulb of Held. Endbulbs are made by AN fibers onto bushy cells (BC) in the anterior ventral cochlear nucleus. Endbulbs are specialized for relaying timing information of the sound with great reliability. The timing information is used for sound localization. High reliability at endbulbs results from high P r . However, high P r also causes endbulbs to depress strongly when activated at normal rates for a prolonged period of time, which reduces fidelity. This raises the question how endbulbs transmit information when activity levels are high for extended periods, such as noisy conditions. One factor important for regulating NP r Q is neural activity. I hypothesized that P r and N change proportionally to the level of neuronal activity. I focused on how prolonged activity can influence P r at the endbulbs. I found that by exposing mice to constant, non-damaging noise, AN synapses changed to facilitating, reflecting low P r . P r recovered back to high after returning animals to normal sound conditions. Quantal size ( Q ) does not change but rather there was a compensatory increase in number of release sites ( N ). In current-clamp recordings, noise-reared BCs had greater spike fidelity even during high rates of synaptic activity. Thus, AN synapses regulate excitability through an activity-dependent, homeostatic mechanism (Chapter 2). To understand how noise rearing can affect sound sensitivity and dynamic range of ANFs and BCs, I performed in vivo recordings of responses of ANFs and BCs to tones in both quiet and loud backgrounds. I hypothesize that increased excitability of ANFs and BCs following noise rearing enhances the sensitivity and dynamic range of ANFs and BCs. I found that prolonged exposure to non-damaging noise enhances sensitivity to tones of both ANFs and BCs in a loud background. This suggests that noise-reared animals have greater sensitivity and more preservation of dynamic range in loud conditions. Another important characteristic of ANFs and BCs is to process timing information of sounds. I examined how noise rearing affected temporal acuity by studying responses to pairs of closely spaced tones. ANFs had slightly-depressed responses to the second tone regardless of rearing conditions. BCs from control animals showed yet greater depression, but from noise-reared animals showed little or no depression at all. This suggests that noise-reared BCs were better able to relay fine temporal aspects of the sound. These results are consistent with the synaptic changes that take place following noise rearing. Increased excitability of ANFs and BCs from noise-reared animals improves perception of sounds even in loud conditions. The changes in the cochlea and AN synapses following noise rearing could affect auditory processing and sound localization (Chapter 3).