SYNAPTIC INTEGRATION AND PLASTICITY IN COMMAND NEURONS

描述(由申请人提供)：本计划的长期目标 是为了理解伴随着行为变化的神经基础 动物社会地位的变化。小龙虾是一个合适的模型，因为 主导、从属和单一(孤立)行为的差异 动物被很好地描述了，并且调节相关的神经回路 行为模式，如逃避，已经得到了很好的研究。《横向巨人》 逃逸回路中的(Lg)中间神经元作为 行为。LG的兴奋性可以被5-羟色胺(5-羟色胺)调节，但信号 这种调节方式取决于动物的社会地位：5-羟色胺有助于 LG在社会优势动物中的反应和在社会中的抑制 下属。5-羟色胺在社交隔离中的作用取决于 它的应用，无论是快还是慢，在更高或更低的位置 浓度，以及更短或更长的时间。这些最后的影响， 都具有明显的临床相关性，推测是由于 通过独立的5-羟色胺受体竞争第二信使通路， 而社会地位的影响可能是人口变化的结果 不同动物体内可用的受体。因此，第一个目标是 这项提议是为了描述一组调节LG的5-羟色胺受体 小龙虾中枢神经系统5-羟色胺的克隆、测序及表达 感受器。然后，这些受体的抗体将揭示它们的位置，并且 选择性激动剂和拮抗剂的发现将使它们的不同 作用待定，cAMP介导5-羟色胺对LG的一种作用；另一种作用 将确定信使路径并研究它们之间的相互作用 特定激动剂和拮抗剂的使用 细胞外或注射到巨型神经元内。5-羟色胺的长期疗效之一 促进，也是由反复的感觉神经刺激产生的； 这种刺激模式也被认为能引起5-羟色胺的释放。另一个目标 将确定5-羟色胺的释放是否介导了刺激诱导的长期 促进。最后，LG的传入神经是电耦合的；最后 目的是测试这种耦合是否形成一个侧向兴奋网络 在传入中选择和放大到LG的相位输入。这将是 用标准的电生理学技术进行研究。

DESCRIPTION (provided by applicant): The long-term objectives of this proposal are to understand the neural bases for the changes in behavior that accompany changes in an animal's social status. Crayfish are an appropriate model because the differences in the behavior of dominant, subordinate and single (isolated) animals are well described, and the neural circuits that mediate relevant patterns of behavior, such as escape, have been well studied. The Lateral Giant (LG) interneuron in the escape circuit serves as a command neuron for the behavior. LG's excitability can be modulated by serotonin (5HT), but the sign of this modulation depends on the social status of the animal: 5HT facilitates LG's response in social dominant animals and inhibits it in social subordinates. The effect of serotonin in social isolates depends on the manner in which it is applied, whether fast or slow, at higher or lower concentrations, and for shorter or longer periods. These last effects, which are of clear clinical relevance, are hypothesized to result from activation of competing second messenger pathways through separate serotonin receptors, whereas the effects of social status may result from changes in the population of available receptors in the different animals. Accordingly, the first aim of the proposal is to describe the set of serotonin receptors that modulate LG's response by cloning, sequencing and expressing crayfish CNS serotonin receptors. Antibodies to those receptors will then reveal their location, and the discovery of selective agonists and antagonists will enable their different effects to be determined, cAMP mediates one effect of 5HT on LG; other 2nd messengers pathways will be identified and their interactions studied through the use of specific agonists and antagonists that can be either applied extracellularly or injected into the giant neuron. One effect of 5HT, long-term facilitation, is also produced by repeated bouts of sensory nerve stimulation; this pattern of stimulation is also known to evoke 5HT release. Another aim will be to determine whether release of 5HT mediates stimulus-induced long-term facilitation. Finally, the afferents to LG are electrically coupled; the final aim will be to test whether this coupling forms a lateral excitatory network among the afferents to select and amplify phasic inputs to LG. This will be studied with standard electrophyiological techniques.