Florida Atlantic University, Department of Biological Sciences, Boca Raton, FL 33431, USA.
International Max-Planck Research School (IMPRS) for Brain and Behavior, Boca Raton, FL 33431, USA.
J Exp Biol. 2018 Jul 18;221(Pt 14):jeb179747. doi: 10.1242/jeb.179747.
is a well-characterized model for neurological disorders and is widely used for investigating causes of altered neuronal excitability leading to seizure-like behavior. One method used to analyze behavioral output of neuronal perturbance is recording the time to locomotor recovery from an electroconvulsive shock. Based on this behavior, we sought to quantify seizure susceptibility in larval with differences in the enzymatic activity levels of a major protein, cGMP-dependent protein kinase (PKG). PKG, encoded by , has two natural allelic variants and has previously been implicated in several important physiological characteristics including: foraging patterns, learning and memory, and environmental stress tolerance. The well-established NO/cGMP/PKG signaling pathway found in the fly, which potentially targets downstream K channel(s), ultimately impacts membrane excitability, leading to our hypothesis: altering PKG enzymatic activity modulates time to recovery from an electroconvulsive seizure. Our results show that by both genetically and pharmacologically increasing PKG enzymatic activity, we can decrease the locomotor recovery time from an electroconvulsive seizure in larval .
是一种神经疾病的典型模型，广泛用于研究导致类似癫痫发作的神经元兴奋性改变的原因。一种用于分析神经元扰动行为输出的方法是记录从电惊厥中运动恢复的时间。基于这种行为，我们试图量化幼虫中的癫痫易感性，幼虫中存在一种主要蛋白质 cGMP 依赖性蛋白激酶 (PKG) 的酶活性水平存在差异。PKG 由 编码，有两个天然等位基因变异体，先前已被牵涉到包括：觅食模式、学习和记忆以及环境压力耐受在内的几个重要生理特征中。在果蝇中发现的成熟的 NO/cGMP/PKG 信号通路，可能靶向下游 K 通道，最终影响膜兴奋性，这导致了我们的假设：改变 PKG 酶活性会调节从电惊厥中恢复的时间。我们的结果表明，通过遗传和药理学方法增加 PKG 酶活性，我们可以缩短幼虫中电惊厥后的运动恢复时间。
