Delgado R, Davis R, Bono M R, Latorre R, Labarca P
Centro de Estudios Cientificos de Santiago, Casilla 16443, Santiago 9, Chile.
J Neurosci. 1998 Feb 15;18(4):1399-407. doi: 10.1523/JNEUROSCI.18-04-01399.1998.
Outward current modulation by cAMP was investigated in wild type (wt) and dunce (dnc) Drosophila larval neurons. dnc is deficient in a cAMP phosphodiesterase and has altered memory. Outward current modulation by cAMP was investigated by acute or chronic exposure to cAMP analogs. The analysis included a scrutiny of outward current modulation by cAMP in neurons from the mushroom bodies (mrb). In Drosophila, the mrb are the centers of olfactory acquisition and retention. Based on outward current patterns, neurons were classified into four types. Downmodulation of outward currents induced by acute application of cAMP analogs was reversible and found only in type I and type IV neurons. In the general wt neuron population, approximately half of neurons exhibited cAMP-modulated, 4-aminopyridine (4-AP)-sensitive currents. On the other hand, a significantly larger fraction of mrb neurons in wt (70%) was endowed with cAMP-modulated, 4-AP-sensitive currents. Only 30% of the dnc neurons displayed outward currents modulated by cAMP. The deficit of cAMP-modulated outward currents was most severe in neurons derived from the mrb of dnc individuals. Only 4% of the mrb neurons of dnc were cAMP-modulated. The dnc defect can be induced by chronic exposure of wt neurons to cAMP analogs. These results document for the first time a well defined electrophysiological neuron phenotype in correlation with the dnc defect. Moreover, this study demonstrates that in dnc mutants such a deficiency affects most severely neurons in brain centers of acquisition and retention.
在野生型（wt）和果蝇迟钝型（dnc）幼虫神经元中研究了环磷酸腺苷（cAMP）对外向电流的调节作用。dnc缺乏一种环磷酸腺苷磷酸二酯酶，且记忆功能发生了改变。通过急性或慢性暴露于环磷酸腺苷类似物来研究cAMP对外向电流的调节作用。分析包括对来自蘑菇体（mrb）的神经元中cAMP对外向电流调节作用的详细审查。在果蝇中，蘑菇体是嗅觉获取和记忆的中心。根据外向电流模式，神经元被分为四种类型。急性应用环磷酸腺苷类似物诱导的外向电流下调是可逆的，且仅在I型和IV型神经元中发现。在野生型神经元总体中，约一半的神经元表现出cAMP调节的、对4 - 氨基吡啶（4 - AP）敏感的电流。另一方面，野生型中显著更大比例（70%）的蘑菇体神经元具有cAMP调节的、对4 - AP敏感的电流。只有30%的dnc神经元显示出受cAMP调节的外向电流。cAMP调节的外向电流缺陷在来自dnc个体蘑菇体的神经元中最为严重。dnc的蘑菇体神经元中只有4%受cAMP调节。野生型神经元长期暴露于环磷酸腺苷类似物可诱发dnc缺陷。这些结果首次记录了一种与dnc缺陷相关的明确的电生理神经元表型。此外，本研究表明，在dnc突变体中，这种缺陷对获取和记忆脑中心的神经元影响最为严重。
