An increase in AMPA and a decrease in SK conductance increase burst firing by different mechanisms in a model of a dopamine neuron in vivo
An increase in AMPA and a decrease in SK conductance increase burst firing by different mechanisms in a model of a dopamine neuron in vivo
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DOI：
10.1152/jn.00704.2006
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发表时间：
2006-11-01
影响因子：
2.5
通讯作者：
Landry, R. S.
中科院分区：
文献类型：
--
作者：
Canavier, C. C.;Landry, R. S.
在体内的多巴胺神经元模型中，AMPA的增加和SK电导的减少通过不同的机制增加了猝发放电。神经生理学杂志96：2549-2563,2006。2006年8月2日首次出版；DOI：10.1152/jn.00704.2006。体内一个程式化的、对称的、隔室的多巴胺神经元模型展示了如何同时或不同地调制速率和模式。如果模型中的两个或两个以上参数同时变化，基线放电率和爆发程度就会变得不相关，这就解释了体内缺乏紧密相关性的原因，并与产生基线放电率与爆发的机制的某种独立性一致。我们假设，大多数突触是由一连串的突触输入触发的，特别有意义的刺激以更同步的方式招募更多数量的突触。并行调制的一个例子是，增加短暂的AMPA电流会引起额外的尖峰，而不考虑模式，从而在尖峰频率和突发发射的比例上产生类似的增加。另一方面，阻断SK电流通过允许先前只产生单个尖峰的去极化引起两个或更多的脉冲，并以相同的原理拉长现有的脉冲，从而引起额外的脉冲，导致对模式的影响大于速率。在激发模式中随机插入尖峰的概率算法对增加AMPA电导而不是通过阻断SK电流而引起的模式变化产生了很好的近似，这与后一种情况下的差分调制是一致的。此外，对模拟的有意义的输入做出反应时，阻断SK会产生更长的脉冲串，具有更高的脉冲串内频率，这表明减少这一电流可能会增强与奖励相关的反应。
An increase in AMPA and a decrease in SK conductance increase burst firing by different mechanisms in a model of a dopamine neuron in vivo. J Neurophysiol 96: 2549-2563, 2006. First published August 2, 2006; doi:10.1152/jn.00704.2006. A stylized, symmetric, compartmental model of a dopamine neuron in vivo shows how rate and pattern can be modulated either concurrently or differentially. If two or more parameters in the model are varied concurrently, the baseline firing rate and the extent of bursting become decorrelated, which provides an explanation for the lack of a tight correlation in vivo and is consistent with some independence of the mechanisms that generate baseline firing rates versus bursts. We hypothesize that most bursts are triggered by a barrage of synaptic input and that particularly meaningful stimuli recruit larger numbers of synapses in a more synchronous way. An example of concurrent modulation is that increasing the short-lived AMPA current evokes additional spikes without regard to pattern, producing comparable increases in spike frequency and fraction fired in bursts. On the other hand, blocking the SK current evokes additional bursts by allowing a depolarization that previously produced only a single spike to elicit two or more and elongates existing bursts by the same principle, resulting in a greater effect on pattern than rate. A probabilistic algorithm for the random insertion of spikes into the firing pattern produces a good approximation to the pattern changes induced by increasing the AMPA conductance, but not by blocking the SK current, consistent with a differential modulation in the latter case. Furthermore, blocking SK produced a longer burst with a greater intra-burst frequency in response to a simulated meaningful input, suggesting that reduction of this current may augment reward-related responses.