Postsynaptic Activity of Type II Cochlear Afferents

点击翻译按钮获取中文摘要

DESCRIPTION (provided by applicant): The cochlea contains two types of primary afferent neurons, the Type I and Type II spiral ganglion neurons. 95% of the spiral ganglion population consists of the Type I neurons, which encode acoustic stimuli. The remaining 5% of the spiral ganglion population, the Type II neurons, ramify extensively among outer hair cells (OHCs). Little is known about their electrical properties as only a few recordings have been performed from the neurons. This lack of functional information precludes hypotheses as to the role of the Type II afferents in perception of auditory stimuli. We have developed a technique that allows gigaohm-seal intracellular recordings in Type II afferent dendrites near their synaptic inputs. Use of a neuronal tracer allows identification of the neurons based upon comparison to the known dendritic morphology well described in the literature. We propose to demonstrate that synaptic inputs to the Type II afferents from OHCs are functional, and to describe the strength of these inputs to Type II neurons. Comparison of the activation induced by synaptic inputs to the threshold for fiber activation as determined within the aims of this proposal will allow estimation of the level of stimulation of OHCs that may be necessary to induce supra-threshold activation of the Type II afferent. Electrophysiological parameters of the Type II dendrite will be incorporated into a cable model of the neuron. This can be used to determine the likelihood that stimuli will produce enough activation of the dendritic field to generate action potentials that may then be transmitted centrally to be incorporated into our perception of auditory stimuli. Purines stimulate the Type II afferents, both directly and by eliciting synaptic input from OHCs (preliminary data). While ATP serves many purposes, it can also be released from damaged cells and may be involved in signaling of cell damage in response to loud sounds. Other compounds implicated in cellular damage will be tested for their ability to activate Type II dendrites to further probe this hypothesis. Further, we will begin to describe processes by which the neurons are sensitized. Activation of UTP, an agonist at metabotropic P2Y receptors, stimulates Type II dendrites. Therefore, we will use pharmacological tools to manipulate second messenger pathways that may be downstream of P2Y activation in order to determine their role in Type II dendrite excitability. We will also test other compounds that may similarly initiate these second messenger cascades, such as Substance P, for their actions on activation and sensitization of Type II afferent dendrites. Prior to preliminary data presented for this proposal, nearly nothing was known regarding the activity in response to stimuli of one of the only two classes of primary auditory neurons. Therefore, analysis of the functions of Type II afferent neurons is crucial to a broader understanding of perception of sound. PUBLIC HEALTH RELEVANCE: The cochlea contains two types of neurons that transmit sensory information to the central nervous system, the Type I neurons which carry the acoustic information of sound timing, intensity and frequency, and the poorly understood Type II neurons about which little is known. This research proposal aims to develop techniques to measure electrical activity within the Type II neurons, which may enable a determination of their functional roles. An understanding of responses of both classes of auditory neurons is necessary for a complete understanding of perception of sound.