Reliable neuromodulation from circuits with variable underlying structure
Reliable neuromodulation from circuits with variable underlying structure
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DOI：
10.1073/pnas.0905614106
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发表时间：
2009-07-14
影响因子：
11.1
通讯作者：
Marder, Eve
中科院分区：
文献类型：
--
作者：
Grashow, Rachel;Brookings, Ted;Marder, Eve
最近的研究认为，相似的网络性能可能是由高度可变的网络参数集产生的，这就提出了一个问题：神经调节在具有不同突触强度和内在膜电导的网络的个体之间是否可靠。为了解决这个问题，我们使用动态钳从蟹口胃神经节的胃磨（GM）神经元构建2细胞相互抑制网络。当人工抑制突触 (g(syn)) 的强度和人工 I-h (g(h)) 的电导随动态钳位变化时，会产生各种网络行为，包括稳定交替爆发的区域。在生理盐水中构建网络输出作为 g(syn) 和 g(h) 函数的图，并在血清素或氧化震颤素存在下再次构建。血清素和氧化震颤素都可以去极化并兴奋孤立的单个 GM 神经元，但通过不同的细胞机制。血清素和氧化震颤素均增加了支持交替爆发的参数区域的大小，并且平均而言增加了爆发频率。尽管如此，在这两种情况下，样本空间内的一些参数集偏离了平均总体响应并且频率下降。这些数据让我们深入了解为什么对大多数个体有效的药物治疗会对少数个体产生异常行为，并且它们对于理解神经系统的进化具有重要意义。
Recent work argues that similar network performance can result from highly variable sets of network parameters, raising the question of whether neuromodulation can be reliable across individuals with networks with different sets of synaptic strengths and intrinsic membrane conductances. To address this question, we used the dynamic clamp to construct 2-cell reciprocally inhibitory networks from gastric mill (GM) neurons of the crab stomatogastric ganglion. When the strength of the artificial inhibitory synapses (g(syn)) and the conductance of an artificial I-h (g(h)) were varied with the dynamic clamp, a variety of network behaviors resulted, including regions of stable alternating bursting. Maps of network output as a function of g(syn) and g(h) were constructed in normal saline and again in the presence of serotonin or oxotremorine. Both serotonin and oxotremorine depolarize and excite isolated individual GM neurons, but by different cellular mechanisms. Serotonin and oxotremorine each increased the size of the parameter regions that supported alternating bursting, and, on average, increased burst frequency. Nonetheless, in both cases some parameter sets within the sample space deviated from the mean population response and decreased in frequency. These data provide insight into why pharmacological treatments that work in most individuals can generate anomalous actions in a few individuals, and they have implications for understanding the evolution of nervous systems.