Inhibitory Control of Synaptic and Behavioral Plasticity by Octopaminergic Signaling
Inhibitory Control of Synaptic and Behavioral Plasticity by Octopaminergic Signaling
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DOI：
10.1523/jneurosci.6517-11.2012
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发表时间：
2012-05-02
影响因子：
5.3
通讯作者：
Budnik, Vivian
中科院分区：
文献类型：
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作者：
Koon, Alex C.;Budnik, Vivian
肾上腺素能受体及其配体是突触可塑性和后可塑性的重要调节因子，但其作用的确切机制仍然知之甚少。章鱼胺是哺乳动物肾上腺素或去甲肾上腺素的无脊椎动物同系物，在调节行为和突触功能中起重要作用。我们以前发现了一个章鱼胺能正反馈机制，以调节结构突触可塑性在发展过程中，并在饥饿的反应。在这种机制下，Octbeta 2R自身受体的激活章鱼胺在章鱼胺能神经元启动cAMP依赖性级联反应，刺激果蝇幼虫神经肌肉接头（NMJ）的新的突触结的发展。然而，用来阻止这种积极反馈的监管机制尚不清楚。在这里，我们报告的替代章鱼胺自身受体，Oct β 1R，突触生长拮抗功能的存在。oct β 1r的突变导致多巴胺能和章鱼胺能NMJ的过度生长，表明Oct β 1R是突触扩张的负调节因子。与Oct beta 2R一样，Oct beta 1R在突触前运动神经元中以细胞自主的方式发挥作用。然而，与Oct β 2R不同，Oct β 1R可能通过抑制Go α抑制cAMP的产生。尽管它的抑制作用，Oct β 1R是必需的突触结构的急性变化，响应章鱼胺和饥饿诱导的运动速度的增加。这些结果表明章鱼胺对突触生长和行为可塑性的双重作用，并突出了对生理刺激的正常反应的抑制影响的重要作用。
Adrenergic receptors and their ligands are important regulators of synaptic plasticity and metaplasticity, but the exact mechanisms underlying their action are still poorly understood. Octopamine, the invertebrate homolog of mammalian adrenaline or noradrenaline, plays important roles in modulating behavior and synaptic functions. We previously uncovered an octopaminergic positive-feedback mechanism to regulate structural synaptic plasticity during development and in response to starvation. Under this mechanism, activation of Oct beta 2R autoreceptors by octopamine at octopaminergic neurons initiated a cAMP-dependent cascade that stimulated the development of new synaptic boutons at the Drosophila larval neuromuscular junction (NMJ). However, the regulatory mechanisms that served to brake such positive feedback were not known. Here, we report the presence of an alternative octopamine autoreceptor, Oct beta 1R, with antagonistic functions on synaptic growth. Mutations in oct beta 1r result in the overgrowth of both glutamatergic and octopaminergic NMJs, suggesting that Oct beta 1R is a negative regulator of synaptic expansion. As Oct beta 2R, Oct beta 1R functioned in a cell-autonomous manner at presynaptic motorneurons. However, unlike Oct beta 2R, which activated a cAMP pathway, Oct beta 1R likely inhibited cAMP production through inhibitory Go alpha. Despite its inhibitory role, Oct beta 1R was required for acute changes in synaptic structure in response to octopamine and for starvation-induced increase in locomotor speed. These results demonstrate the dual action of octopamine on synaptic growth and behavioral plasticity, and highlight the important role of inhibitory influences for normal responses to physiological stimuli.