Tonic 5nM DA stabilizes neuronal output by enabling bidirectional activity-dependent regulation of the hyperpolarization activated current via PKA and calcineurin.
Tonic 5nM DA stabilizes neuronal output by enabling bidirectional activity-dependent regulation of the hyperpolarization activated current via PKA and calcineurin.
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DOI：
10.1371/journal.pone.0117965
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Baro DJ
中科院分区：
文献类型：
--
作者：
Krenz WD;Rodgers EW;Baro DJ
体积传输产生相位和tonic调制信号。强直性多巴胺（DA）在1型DA受体（D1Rs）上的作用在很大程度上是不明确的。在这里，我们发现5nM强直性DA通过激活超极化激活电流（I h）的活动依赖性调节，在D1Rs处稳定神经元输出数分钟。在5nM DA存在而非不存在的情况下，根据慢波活动的变化调整最大电导（gmax），以维持峰值时间。我们对幽门外侧神经元（LP）的研究表明，当与含有5nM DA的生理盐水混合时，平台持续时间的增量、双向变化会导致LP I hG max的相应变化。然而，当制剂单独与生理盐水混合时，LP I hGmax与占空比之间没有线性相关。因此，强直性nM DA调节了LP I h G max的活性能力；这就是元调制（调制的调制）的例子。用Ca2+螯合剂BAPTA或特异性PKA抑制剂PKI预处理，可以阻止5nM DA中LP I h的所有变化。钙调磷酸酶抑制剂阻断了DA导致的活性依赖性变化，并显示pka介导的LP I hG max活性无关增强。这些数据表明，补品5nM DA同时产生两种pka依赖的效应：直接增加LP I hG max，以及允许钙调磷酸酶调节LP I h的启动事件。后者随着占空比的增加而逐渐降低LP I hG max。我们还证明，当网络输出受到浴池应用的4AP干扰时，这种元调节保留了LP的第一个尖峰的时间。总而言之，5nM DA允许慢波活动提供反馈，维持峰值定时，这表明低电平、强音调制的一个功能是稳定动态输出的特定特征。
Volume transmission results in phasic and tonic modulatory signals. The actions of tonic dopamine (DA) at type 1 DA receptors (D1Rs) are largely undefined. Here we show that tonic 5nM DA acts at D1Rs to stabilize neuronal output over minutes by enabling activity-dependent regulation of the hyperpolarization activated current (I h). In the presence but not absence of 5nM DA, I h maximal conductance (G max) was adjusted according to changes in slow wave activity in order to maintain spike timing. Our study on the lateral pyloric neuron (LP), which undergoes rhythmic oscillations in membrane potential with depolarized plateaus, demonstrated that incremental, bi-directional changes in plateau duration produced corresponding alterations in LP I hG max when preparations were superfused with saline containing 5nM DA. However, when preparations were superfused with saline alone there was no linear correlation between LP I hGmax and duty cycle. Thus, tonic nM DA modulated the capacity for activity to modulate LP I h G max; this exemplifies metamodulation (modulation of modulation). Pretreatment with the Ca2+-chelator, BAPTA, or the specific PKA inhibitor, PKI, prevented all changes in LP I h in 5nM DA. Calcineurin inhibitors blocked activity-dependent changes enabled by DA and revealed a PKA-mediated, activity-independent enhancement of LP I hG max. These data suggested that tonic 5nM DA produced two simultaneous, PKA-dependent effects: a direct increase in LP I h G max and a priming event that permitted calcineurin regulation of LP I h. The latter produced graded reductions in LP I hG max with increasing duty cycles. We also demonstrated that this metamodulation preserved the timing of LP’s first spike when network output was perturbed with bath-applied 4AP. In sum, 5nM DA permits slow wave activity to provide feedback that maintains spike timing, suggesting that one function of low-level, tonic modulation is to stabilize specific features of a dynamic output.
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DOI：
10.1523/jneurosci.3771-09.2010
发表时间：
2010-02-17
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Chen X;Shu S;Schwartz LC;Sun C;Kapur J;Bayliss DA
通讯作者：
Bayliss DA
影响因子：
8.8
作者：
Dittmer PJ;Dell'Acqua ML;Sather WA
通讯作者：
Sather WA
影响因子：
5.5
作者：
Breton, Jean-Didier;Stuart, Greg J.
通讯作者：
Stuart, Greg J.
影响因子：
5.3
作者：
Bucher, D;Prinz, AA;Marder, E
通讯作者：
Marder, E
影响因子：
2.5
作者：
Ayali, A;Johnson, BR;Harris-Warrick, RM
通讯作者：
Harris-Warrick, RM