cGMP mediates short- and long-term modulation of excitability in a decision-making neuron in Aplysia.

cGMP mediates short- and long-term modulation of excitability in a decision-making neuron in Aplysia.
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DOI:
10.1016/j.neulet.2018.06.046
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发表时间:
2018-09-14
影响因子:
2.5
通讯作者:
Mozzachiodi R
Mozzachiodi R
中科院分区:
医学4区
文献类型:
--
作者:
Goldner A;Farruggella J;Wainwright ML;Mozzachiodi R

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在初级神经回路中,兴奋性的变化可以对给定行为的表达产生强烈的影响。B51就是一个例子,它是软体动物海兔(apilsia)进食神经回路中具有决策特性的神经元。B51的兴奋性受内外刺激的双向调节,与相应的摄食行为诱导变化一致。例如,在上调摄食的操作性奖励学习中,B51的兴奋性通过camp依赖机制而增加。相反,在厌恶刺激的训练方案下,B51的兴奋性降低。在这项研究中,我们验证了B51降低兴奋性可能是由另一个环核苷酸cGMP介导的假设。结果表明,cGMP离子电泳注射可诱导B51兴奋性的短期(45 min)和长期(24 h)降低。接下来,我们研究了哪种生化触发因素可以增加cGMP的胞浆水平。神经递质一氧化氮通过激活可溶性胍基环化酶而降低B51的兴奋性。这些发现表明cgmp依赖性通路以与cAMP相反的方式调节B51的兴奋性,表明不同的环核苷酸通路双向调节决策神经元的兴奋性。
In elementary neural circuits, changes in excitability can have a strong impact in the expression of a given behavior. One example is provided by B51, a neuron with decision-making properties in the feeding neural circuit of the mollusk Aplysia. The excitability of B51 is bidirectionally modulated by external and internal stimuli in a manner that is consistent with the corresponding induced changes in feeding behavior. For example, in operant reward learning, which up-regulates feeding, B51 excitability is increased via a cAMP-dependent mechanism. Conversely, following training protocols with aversive stimuli, which down-regulate feeding, B51 excitability is decreased. In this study, we tested the hypothesis that B51 decreased excitability may be mediated by another cyclic nucleotide, cGMP. Our results revealed that iontophoretic injection of cGMP was capable of inducing both short-term (45 min) and long-term (24 h) reduction of B51 excitability. We next investigated which biochemical trigger could increase cGMP cytosolic levels. The neurotransmitter nitric oxide was found to decrease B51 excitability through the activation of the soluble guanylyl cyclase. These findings indicate that a cGMP-dependent pathway modulates B51 excitability in a manner opposite of cAMP, indicating that distinct cyclic-nucleotide pathways bidirectionally regulate the excitability of a decision-making neuron.
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