SYNAPTIC TRANSMISSION DURING NEURONAL DIFFERENTIATION

神经元分化过程中的突触传递

• 批准号: 2126168
• 负责人: Kenna D Peusner
• 金额: $ 22.84万
• 依托单位: GEORGE WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-04-01 至 1998-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2126168
• 关键词: chick embryo; chickens; developmental neurobiology; experimental brain lesion; gamma aminobutyrate; gap junctions; glutamate receptor; immunocytochemistry; membrane channels; motor neurons; neural plasticity; neural transmission; neuroanatomy; neurogenesis; neuropharmacology; newborn animals; synapses; tetanus toxin; vestibular nerve; vestibular pathway; vestibuloocular reflex; voltage /patch clamp

The major theme of this work is to characterize the functional and structural plasticity of synapses formed by the primary vestibular fibers on vestibular sensory neurons in the brainstem during development and to characterize the properties of these vestibular neurons after vestibular neurectomy. All studies will be performed on slice preparations of the tangential vestibular nucleus (TN), part of the chick lateral vestibular nucleus. The largest diameter primary vestibular fibers, or colossal fibers, form large axosomatic endings-the spoon endings- on the TN principal cells. The work is focused on two ages: l) embryonic days 15/16, when gap junctions join chemical synapses to form "mixed synapses" at the spoon endings, and 2) newborns, when the gap junctions are functional at the spoon endings. The techniques used will include intracellular current and voltage clamp, intracellular dye injection, electron microscopy, and immunocytochemistry. The specific aims are to: characterize the developmental appearance of functional gap junctions at spoon synapses; define the vestibular synaptic currents generated at vestibular sensory neurons; determine the plasticity of vestibular synapses in response to tetanus and pharmacologic agents; study the membrane and synaptic properties of neurons in the ipsi- and contralateral TN after unilateral vestibular neurectomy; inject dyes intracellularly to study transient electrical coupling between vestibular neurons and determine whether TN axons project to motor neuron pools in a pattern reflecting inputs from primary vestibular fibers; and identify immunocytochemically gap junction connexins, glutamate receptors and GABA- containing terminals in the developing TN. As we learn more about the factors influencing vestibular synaptic change, we can apply this to enhance or promote new synapse formation to replace central synapses lost to disease, injury or aging. Second, it is important to study synaptic transmission so that the action of drugs on central vestibular synapses can be clarified. Third, this work will add new information on vestibular anatomy which is important to devise models on vestibular system function. Finally, we will apply multiple approaches to analyze the function of neuronal gap junctions. As gap junctions are known to exist in almost every major CNS pathway, it is meaningful to determine the specific roles that gap junctions play in the genesis and function of the central neural circuitry.

这项工作的主要主题是描述功能和 初级前庭纤维形成的突触的结构可塑性 前庭感觉神经元在脑干发育过程中， 表征这些前庭神经元的特性后，前庭 神经切除术 所有研究均将在切线方向的切片制备物上进行。 前庭神经核（TN），鸡前庭外侧核的一部分。的 直径最大的初级前庭纤维，或巨大纤维， TN主细胞上有轴体终末-匙形终末。工作 主要集中在两个年龄：1）胚胎15/16天，当缝隙连接时， 化学突触在匙形末端形成“混合突触”，以及2） 新生儿，当差距连接在匙状末端起作用时。的 所使用的技术将包括细胞内电流和电压钳， 细胞内染料注射、电子显微镜和免疫细胞化学。 其具体目标是： 匙形突触的功能性缝隙连接;定义前庭突触 前庭感觉神经元产生的电流;决定可塑性 前庭突触对破伤风和药物的反应; 研究ipsi中神经元的膜和突触特性， 单侧前庭神经切除术后对侧TN;注射染料 在细胞内研究前庭神经元之间的瞬时电耦合， 神经元和确定是否TN轴突项目的运动神经元池在一个 反映初级前庭纤维输入的模式;并识别 免疫细胞化学间隙连接连接蛋白，谷氨酸受体和GABA- 在显影TN中含有端子。 随着我们对影响前庭突触变化的因素的了解越来越多， 我们可以用它来增强或促进新突触的形成， 由于疾病、损伤或衰老而丧失的中央突触。第二，重要的是 研究突触传递，以便药物对中枢神经系统的作用 前庭突触可以被阐明。三是这项工作将新增 前庭解剖学的信息，这是重要的设计模型， 前庭系统功能最后，我们将采用多种方法， 分析神经元缝隙连接的功能。由于缝隙连接是已知的 存在于几乎每一个主要的中枢神经系统途径，这是有意义的，以确定 缝隙连接在肿瘤的发生和功能中的特殊作用， 中枢神经回路