Presynaptic Mechanisms Responsible for Synaptic Differentiation

IBN 98-08631库珀 神经细胞（“神经元”）与其他细胞在称为突触的形态学上识别的位置化学整合。 一个神经元对它的突触目标有多大的影响是不一样的。 神经元突触效能差异的特征受其内在活动的影响。 不同水平的活动调节突触结构和性能的长期改变。 动物体内有一些内源性的化学物质，即“神经调质”，可以增强或抑制突触的功效。 这些反过来又会影响动物的行为。 神经调节剂通过刺激由不同种类的配体受体（神经调节剂特异性识别和结合的细胞膜中的蛋白质分子）介导的各种信号级联来影响细胞过程。这种变化被认为在学习和记忆以及行为中发挥作用。本研究有两个目的：1）确定神经调节剂是否以不同方式急性影响不同的神经肌肉突触（从神经元到肌肉细胞的突触，神经系统通过这些突触引起肌肉收缩），以及2）检查神经调节剂对这些突触的长期生理和解剖学影响。甲壳类动物的神经系统之所以被使用，是因为它很容易在这一领域进行实验。可以分析识别的单个细胞上的单个突触的活性，可以标记突触和细胞，并且可以稍后通过电子显微镜识别相同的突触用于结构研究。这里描述的小龙虾模型系统提供了已识别的单细胞的单个突触的结构和功能的直接相关性。这种模型神经系统不仅可以评估神经调质对特征明确的行为的影响，而且还允许识别的突触和某些行为组件之间的直接相关性。它允许识别负责突触分化的各种表现的特定细胞机制。 在这一领域的进展将提供一个更清晰的一般性理解的机制，神经调节剂通过改变神经系统的精细结构和细胞生理学改变行为。该项目将研究神经调质如何改变突触功效，影响运动神经元的结构和功能，并将分析这些变化如何影响它们所支配的肌肉。

IBN 98-08631 COOPER The nerve cell ("neuron") is chemically integrated with other cells at morphologically-identified locations called synapses. Just how much effect a neuron has on its synaptic targets varies. The characteristics of neurons' differences in synaptic efficacy are affected by their intrinsic activity. Different levels of activity modulate long-term alterations in both structure and performance of synapses. There are chemicals, "neuromodulators," endogenously released within an animal, which may enhance or suppress synaptic efficacy. These in turn affect the animal's behavior. Neuromodulators affect cellular processes by stimulating various signaling cascades mediated by different classes of ligand receptors (protein molecules in the cell membrane which neuromodulators specifically recognizes and bind to). Such changes are believed to play roles in learning and memory, as well as in behavior. There are two objectives to the present study: 1) to determine if neuromodulators acutely affect different neuromuscular synapses (synapses from neurons onto muscle cells, through which the nervous system causes muscles to contract) differently, and 2) to examine the long-term physiological and anatomical effects neuromodulators have on such synapses. The crustacean nervous system is being used because it easily lends itself to experimentation in this area. The activity of individual synapses on identified single cells can be analyzed, the synapses and cells can be marked, and the same synapses can be identified later for structural investigation by electron microscopy. The crayfish model systems described here provide direct correlation of structure and function at individual synapses of identified single cells. This model nervous system not only makes it possible to assess effects of neuromodulators on well-characterized behaviors, but it also allows direct correlation between identified synapses and certain behavioral components. It permits the ide ntification of specific cellular mechanisms responsible for the various manifestations of synaptic differentiation. Progress in this area will provide a clearer general understanding of the mechanisms by which neuromodulators modify behavior by altering the fine structure and cellular physiology of the nervous system. The project will examine how altering synaptic efficacy by neuromodulators affects motor neuron structure and function, and will analyze how these changes affect the muscles they innervate.