SYNAPTIC INTEGRATION AND PLASTICITY IN COMMAND NEURONS

描述（由申请人提供）：本提案的长期目标 是为了了解伴随着这些变化的行为的神经基础 动物社会地位的变化。小龙虾是一个合适的模型， 支配、从属和单独（孤立）行为的差异 动物被很好地描述了，并且介导相关的神经回路 行为模式，如逃跑，已经得到了很好的研究。横向巨人 (LG)逃逸回路中的中间神经元充当了 行为5-羟色胺（5-HT）可调节LG的兴奋性，但其信号 这种调节取决于动物的社会地位：5 HT促进 LG在社会优势动物中的反应和在社会优势动物中的抑制作用 下属5-羟色胺在社会隔离中的作用取决于 无论是快的还是慢的，无论是高的还是低的， 浓度，以及更短或更长的时间。这些最后的影响， 具有明确的临床相关性，假设是由激活 通过不同的血清素受体竞争第二信使途径， 而社会地位的影响可能来自人口的变化 不同动物体内的可用受体。因此，第一个目标 该计划旨在描述一组调节LG的血清素受体 克隆、测序和表达小龙虾中枢神经系统5-羟色胺 受体。这些受体的抗体将揭示它们的位置， 选择性激动剂和拮抗剂的发现将使它们的不同 作用有待确定，cAMP介导5 HT对LG的一种作用;其他第二种作用 信使途径将被确定，并通过研究它们的相互作用， 使用特异性激动剂和拮抗剂 细胞外或注射到巨大的神经元。5 HT的一种效应，长期 易化，也是由感觉神经刺激的反复发作产生的; 这种刺激模式也已知引起5 HT释放。另一个目的 将确定5-HT的释放是否介导刺激诱导的长期 便利化最后，LG的传入神经是电耦合的; 目的是测试这种耦合是否形成了一个横向兴奋网络 在传入神经中选择和放大对LG的相位输入。这将是 用标准的电泳技术研究。

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.