Ion channels to inactivate neurons in Drosophila.
Ion channels to inactivate neurons in Drosophila.
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DOI：
10.3389/neuro.02.013.2009
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发表时间：
2009
影响因子：
4.8
通讯作者：
Hodge JJ
中科院分区：
文献类型：
--
作者：
Hodge JJ
离子通道是兴奋性的决定因素；因此，操纵它们的水平和性质为研究者提供了调节神经元和电路功能的机会。有许多方法可以抑制果蝇神经元的电活动，例如，在静息膜电位下开放的钾通道（即Shaker Kv1， Shaw Kv3, Kir2.1和DORK）的过度表达。这将导致钾外排增加和膜超极化，使静息膜电位低于激发动作电位所需的阈值。另外，其他通道、泵或共转运蛋白的过度表达也会导致膜电位的超极化，从而阻止放电。最后，通过干扰或降低介导动作电位去极化阶段的功能电压门控钠（Nav1麻痹）或钙（Cav2不和谐）通道的水平，可以使神经元失活。同样，涉及反向通道操作的策略应该允许给定神经元的净去极化和超兴奋。这些离子通道表达的变化可以通过果蝇中可用的通用转基因（即基于Gal4/UAS的）系统来实现，这些系统可以对（通道）转基因表达进行精细的时间和空间控制。这些系统使得电灭活（或过度激活）果蝇大脑中的任何神经元或神经回路成为可能，就像一个精致的损伤实验，有可能阐明每个网络介导的任何有趣的行为或表型。这些技术现在正在果蝇身上被用于重新编程定义良好的电路的电活动，并在行为上带来稳健且易于量化的变化，从而允许不同的模型和假设得到快速测试。
Ion channels are the determinants of excitability; therefore, manipulation of their levels and properties provides an opportunity for the investigator to modulate neuronal and circuit function. There are a number of ways to suppress electrical activity in Drosophila neurons, for instance, over-expression of potassium channels (i.e. Shaker Kv1, Shaw Kv3, Kir2.1 and DORK) that are open at resting membrane potential. This will result in increased potassium efflux and membrane hyperpolarisation setting resting membrane potential below the threshold required to fire action potentials. Alternatively over-expression of other channels, pumps or co-transporters that result in a hyperpolarised membrane potential will also prevent firing. Lastly, neurons can be inactivated by, disrupting or reducing the level of functional voltage-gated sodium (Nav1 paralytic) or calcium (Cav2 cacophony) channels that mediate the depolarisation phase of action potentials. Similarly, strategies involving the opposite channel manipulation should allow net depolarisation and hyperexcitation in a given neuron. These changes in ion channel expression can be brought about by the versatile transgenic (i.e. Gal4/UAS based) systems available in Drosophila allowing fine temporal and spatial control of (channel) transgene expression. These systems are making it possible to electrically inactivate (or hyperexcite) any neuron or neural circuit in the fly brain, and much like an exquisite lesion experiment, potentially elucidate whatever interesting behaviour or phenotype each network mediates. These techniques are now being used in Drosophila to reprogram electrical activity of well-defined circuits and bring about robust and easily quantifiable changes in behaviour, allowing different models and hypotheses to be rapidly tested.
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DOI：
10.1126/science.1166673
发表时间：
2009-04-03
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Gilestro GF;Tononi G;Cirelli C
通讯作者：
Cirelli C
影响因子：
16.2
作者：
Haghighi, AP;McCabe, BD;Goodman, CS
通讯作者：
Goodman, CS
影响因子：
11.4
作者：
GISSELMANN, G;SEWING, S;PONGS, O
通讯作者：
PONGS, O
影响因子：
16.2
作者：
Gordon, Michael D.;Scott, Kristin
通讯作者：
Scott, Kristin
影响因子：
5.3
作者：
Cao, Guan;Nitabach, Michael N.
通讯作者：
Nitabach, Michael N.