Cell-specific Synaptic and Intrinsic Plasticity of Auditory Cortical Neurons after Noise Exposure

项目总结/文摘

Project Summary/Abstract Exposure to loud sound induces death of cochlear hair cells and loss of synapses between hair cells and the auditory nerve, which contribute to loss of afferent input to the brain. While a reduction of input, as a result of noise exposure, may be predicted to cause reduced responses to sound, it paradoxically increases excitatory responses in auditory cortex. The observed increase in excitatory responses serves an adaptive function, such that increased responsiveness to sound aids perception even with reduced input from the auditory periphery. This phenomenon has been termed auditory gain adaptation. A decrease in parvalbumin (PV) neuron- mediated inhibition to principal neurons has been suggested as a possible mechanism for gain adaptation after noise exposure. However, the mechanisms of intrinsic and synaptic plasticity in auditory cortex after noise exposure are unknown. Our preliminary, in vivo calcium imaging results, demonstrate that PV neurons increase their gain in response to sound after noise exposure, while auditory cortical slice results show a depolarization of the resting membrane potential of PV neurons. Furthermore, these plastic changes occur in PV neurons before principal neurons. By determining the synaptic and intrinsic mechanisms of plasticity of PV and principal neurons, we will understand how the seemingly counterintuitive increases in PV gain and intrinsic excitability ultimately result in increased excitatory gain after noise exposure. I aim to test the hypothesis that noise exposure induces plasticity in auditory cortex that involves time-dependent increases in PV and principal neuron intrinsic excitability, as well as synapse-specific changes in their synaptic contacts. Thus, by utilizing a combination of optogenetics, whole-cell electrophysiology, and in vivo Auditory Brainstem Response (ABR) and Distortion Product Otoacoustic Emission (DPOAE) measurements, this proposal aims to test this hypothesis. Furthermore, this proposal aims to investigate the noise exposure conditions in which plasticity occurs, and conduct a detailed investigation of the time course of plasticity in a cell and layer-specific manner. Results from this proposal will provide insight to the adult plasticity mechanisms of auditory cortex after noise exposure. The expected outcome of this proposal may identify potential therapeutic targets of disorders implicated in pathological increases of gain, such as tinnitus and hyperacusis, and aid our understanding of adult plasticity in auditory cortex.