SYNAPTIC TRANSMISSION DURING NEURONAL DIFFERENTIATION

这项工作的主要目的是更好地了解前庭核神经元信号处理发展的基本机制，以及这种兴奋性在外周前庭损伤后如何变化。鸡的切线核(前庭外侧核)将在胚胎和新生年龄用脑片和整个动物进行研究。选择这个核团是因为它相当简单和众所周知的解剖结构，包括这个核团的两个主要神经元群在两个前庭反射中发挥作用的事实。在这个系统中，关于神经元的形态发生和初级前庭纤维的突触发生已经有了丰富的知识。此外，幼年动物有很高的可塑性，在鸡身上进行前庭去传入相对容易。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，外向膜片记录，药理学，以及光和免疫金电子显微镜免疫细胞化学。其具体目的包括表征和量化新生儿发育过程中和前庭神经切断后切核神经元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。通过应用多种方法分析已识别的前庭核神经元的结构-功能关系，我们将阐明不同类型的神经元在前庭信号处理中所扮演的角色。此外，随着我们对前庭核神经元兴奋性和突触传递的基本机制有更多的了解，我们可以将其应用于改进由疾病、损伤或衰老引起的中枢性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.