Engel J E, Wu C F
Department of Biological Sciences, University of Iowa, Iowa City, Iowa 52242, USA.
J Neurosci. 1998 Mar 15;18(6):2254-67. doi: 10.1523/JNEUROSCI.18-06-02254.1998.
Potassium channels have been implicated in central roles in activity-dependent neural plasticity. The giant fiber escape pathway of Drosophila has been established as a model for analyzing habituation and its modification by memory mutations in an identified circuit. Several genes in Drosophila encoding K+ channel subunits have been characterized, permitting examination of the contributions of specific channel subunits to simple conditioning in an identified circuit that is amenable to genetic analysis. Our results show that mutations altering each of four K+ channel subunits (Sh, slo, eag, and Hk) have distinct effects on habituation at least as strong as those of dunce and rutabaga, memory mutants with defective cAMP metabolism (). Habituation, spontaneous recovery, and dishabituation of the electrically stimulated long-latency giant fiber pathway response were shown in each mutant type. Mutations of Sh (voltage-gated) and slo (Ca2+-gated) subunits enhanced and slowed habituation, respectively. However, mutations of eag and Hk subunits, which confer K+-current modulation, had even more extreme phenotypes, again enhancing and slowing habituation, respectively. In double mutants, Sh mutations moderated the strong phenotypes of eag and Hk, suggesting that their modulatory functions are best expressed in the presence of intact Sh subunits. Nonactivity-dependent responses (refractory period and latency) at two stages of the circuit were altered only in some mutants and do not account for modifications of habituation. Furthermore, failures of the long-latency response during habituation, which normally occur in labile connections in the brain, could be induced in the thoracic circuit stage in Hk mutants. Our work indicates that different K+ channel subunits play distinct roles in activity-dependent neural plasticity and thus can be incorporated along with second messenger "memory" loci to enrich the genetic analysis of learning and memory.
钾通道在依赖活动的神经可塑性中发挥着核心作用。果蝇的巨纤维逃逸通路已被确立为分析习惯化及其在特定回路中因记忆突变而发生改变的模型。果蝇中几个编码钾离子通道亚基的基因已得到表征，这使得在一个适合进行遗传分析的特定回路中，能够研究特定通道亚基对简单条件反射的作用。我们的结果表明，改变四个钾离子通道亚基（Sh、slo、eag和Hk）中每一个的突变对习惯化都有明显影响，其影响程度至少与dunce和rutabaga（cAMP代谢有缺陷的记忆突变体）相同。在每种突变类型中都展示了电刺激的长潜伏期巨纤维通路反应的习惯化、自发恢复和去习惯化。Sh（电压门控）和slo（钙门控）亚基的突变分别增强和减缓了习惯化。然而，赋予钾电流调制功能的eag和Hk亚基的突变具有更为极端的表型，同样分别增强和减缓了习惯化。在双突变体中，Sh突变缓和了eag和Hk的强烈表型，这表明它们的调节功能在完整的Sh亚基存在时能得到最佳表达。该回路两个阶段的非依赖活动的反应（不应期和潜伏期）仅在某些突变体中发生改变，且无法解释习惯化的改变。此外，在习惯化过程中长潜伏期反应的失败（通常发生在大脑中不稳定的连接中）在Hk突变体的胸段回路阶段能够被诱导产生。我们的工作表明，不同的钾离子通道亚基在依赖活动的神经可塑性中发挥着不同的作用，因此可以与第二信使“记忆”位点一起纳入，以丰富对学习和记忆的遗传分析。
