SYNAPTIC TRANSMISSION DURING NEURONAL DIFFERENTIATION

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The major goal of this work is to better understand the fundamental mechanisms involved in the development of signal processing by vestibular nuclei neurons, and how this excitability changes after peripheral vestibular injury. The chick tangential nucleus (lateral vestibular nucleus) will be investigated using brain slices and whole animals at embryonic and newborn ages. This nucleus was chosen due to its rather simple and well-known anatomy, including the fact that the two main neuron populations of this nucleus function in two of the vestibular reflexes. Already, there is a wealth of knowledge existing on neuron morphogenesis and synaptogenesis by the primary vestibular fibers in this system. Further, there is a high degree of plasticity in young animals and it is relatively easy to perform vestibular deafferentations in the chicken. The techniques applied will include whole-cell patch-clamp recordings in current- and voltage-clamp modes, outside-out patch recordings, pharmacology, and light and immunogold electron- microscopic immunocytochemistry. The specific aims include to characterize and quantify the voltage-gated outward potassium currents, vestibular synaptic currents, excitability, and glutamate neurotransmission in tangential nucleus neurons during development and after vestibular-nerve transection in the newborn. By applying multiple approaches to analyze the structure-function relationships of identified vestibular nuclei neurons, we will clarify the roles that different neuron classes play in vestibular signal processing. In addition, as we learn more about the basic mechanisms involved in excitability and synaptic transmission by vestibular nuclei neurons, we can apply this to improve drug treatments for central vestibular disorders resulting from disease, injury or aging.