SYNAPTIC TRANSMISSION DURING NEURONAL DIFFERENTIATION

这项工作的主要目标是更好地了解前庭核神经元信号处理的发展所涉及的基本机制，以及外周前庭损伤后这种兴奋性如何变化。 将使用胚胎和新生儿年龄的脑切片和整个动物研究鸡的切向核（前庭外侧核）。 选择这个核是因为它相当简单和众所周知的解剖结构，包括这个核的两个主要神经元群体在两个前庭反射中起作用的事实。 已经有大量的知识存在于这个系统中的初级前庭纤维的神经元形态发生和突触发生。 此外，幼年动物具有高度的可塑性，在鸡中进行前庭传入神经阻滞相对容易。 应用的技术将包括电流和电压钳模式下的全细胞膜片钳记录、外向膜片钳记录、药理学以及光和免疫金电子显微镜免疫细胞化学。 具体的目标包括表征和量化的电压门控外向钾电流，前庭突触电流，兴奋性，和谷氨酸神经传递的切向核神经元在发展过程中和前庭神经横断后的新生儿。通过应用多种方法来分析前庭核神经元的结构-功能关系，我们将阐明不同神经元类别在前庭信号处理中所起的作用。 此外，随着我们更多地了解前庭核神经元兴奋性和突触传递的基本机制，我们可以将其应用于改善由疾病，损伤或衰老引起的中枢前庭疾病的药物治疗。

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.