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首页> 外文期刊>The European Journal of Neuroscience >Suppression of inhibitory GABAergic transmission by cAMP signaling pathway: Alterations in learning and memory mutants
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Suppression of inhibitory GABAergic transmission by cAMP signaling pathway: Alterations in learning and memory mutants

机译：通过cAMP信号通路抑制抑制性GABA能传递：学习和记忆突变体的变化。

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The cAMP signaling pathway mediates synaptic plasticity and is essential for memory formation in both vertebrates and invertebrates. In the fruit fly Drosophila melanogaster, mutations in the cAMP pathway lead to impaired olfactory learning. These mutant genes are preferentially expressed in the mushroom body (MB), an anatomical structure essential for learning. While cAMP-mediated synaptic plasticity is known to be involved in facilitation at the excitatory synapses, little is known about its function in GABAergic synaptic plasticity and learning. In this study, using whole-cell patch-clamp techniques on Drosophila primary neuronal cultures, we demonstrate that focal application of an adenylate cyclase activator forskolin (FSK) suppressed inhibitory GABAergic postsynaptic currents (IPSCs). We observed a dual regulatory role of FSK on GABAergic transmission, where it increases overall excitability at GABAergic synapses, while simultaneously acting on postsynaptic GABA receptors to suppress GABAergic IPSCs. Further, we show that cAMP decreased GABAergic IPSCs in a PKA-dependent manner through a postsynaptic mechanism. PKA acts through the modulation of ionotropic GABA receptor sensitivity to the neurotransmitter GABA. This regulation of GABAergic IPSCs is altered in the cAMP pathway and short-term memory mutants dunce and rutabaga, with both showing altered GABA receptor sensitivity. Interestingly, this effect is also conserved in the MB neurons of both these mutants. Thus, our study suggests that alterations in cAMP-mediated GABAergic plasticity, particularly in the MB neurons of cAMP mutants, account for their defects in olfactory learning. Drosophila inhibitory GABAergic postsynaptic currents (IPSCs) are suppressed by forskolin (FSK) and PKA activation (see below). This regulation of GABAergic IPSCs is altered in the cAMP pathway and short-term memory mutants dunce and rutabaga, with both showing altered GABA receptor sensitivity.
机译：cAMP信号通路介导突触可塑性，对于脊椎动物和无脊椎动物的记忆形成至关重要。在果蝇果蝇中，cAMP途径中的突变导致嗅觉学习受损。这些突变基因优先在蘑菇体（MB）中表达，蘑菇体是学习所必需的解剖结构。虽然已知cAMP介导的突触可塑性参与了兴奋性突触的促进作用，但对其在GABA能突触可塑性和学习中的功能知之甚少。在这项研究中，使用果蝇原代神经元文化的全细胞膜片钳技术，我们证明了腺苷酸环化酶激活剂福斯高林（FSK）的焦点应用抑制抑制性GABA能突触后电流（IPSCs）。我们观察到FSK对GABA能传递具有双重调节作用，它在GABA能突触处增加总体兴奋性，同时作用于突触后GABA受体以抑制GABA能IPSC。此外，我们表明，cAMP通过突触后机制以PKA依赖性方式降低GABA能IPSC。 PKA通过调节离子性GABA受体对神经递质GABA的敏感性来发挥作用。 GABA能性IPSC的这种调节在cAMP途径和短期记忆突变体dunce和rutabaga中发生了改变，均显示出改变的GABA受体敏感性。有趣的是，在这两个突变体的MB神经元中也保持了这种效应。因此，我们的研究表明，cAMP介导的GABA能塑性，特别是cAMP突变体的MB神经元的改变，解释了它们在嗅觉学习中的缺陷。果蝇抑制性GABA能突触后电流（IPSCs）被毛喉素（FSK）和PKA激活抑制（见下文）。 GABA能性IPSC的这种调节在cAMP途径和短期记忆突变体dunce和rutabaga中发生了改变，都显示出改变的GABA受体敏感性。

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