Distinctions among electroconvulsion- and proconvulsant-induced seizure discharges and native motor patterns during flight and grooming: quantitative spike pattern analysis in <i>Drosophila</i> flight muscles

In <i>Drosophila</i>, high-frequency electrical stimulation across the brain triggers a highly stereotypic repertoire of spasms. These electroconvulsive seizures (ECS) manifest as distinctive spiking discharges across the nervous system and can be stably assessed throughout the seizure repertoire in the large indirect flight muscles dorsal longitudinal muscles (DLMs) to characterize modifications in seizure-prone mutants. However, the relationships between ECS-spike patterns and native motor programs, including flight and grooming, are not known and their similarities and distinctions remain to be characterized. We employed quantitative spike pattern analyses for the three motor patterns including: (1) overall firing frequency, (2) spike timing between contralateral fibers, and (3) short-term variability in spike interval regularity (CV₂) and instantaneous firing frequency (ISI⁻¹). This base-line information from wild-type (WT) flies facilitated quantitative characterization of mutational effects of major neurotransmitter systems: excitatory cholinergic (<i>Cha</i>), inhibitory GABAergic (<i>Rdl</i>) and electrical (<i>ShakB</i>) synaptic transmission. The results provide an initial glimpse on the vulnerability of individual motor patterns to different perturbations. We found marked alterations of ECS discharge spike patterns in terms of either seizure threshold, spike frequency or spiking regularity. In contrast, no gross alterations during grooming and a small but noticeable reduction of firing frequency during <i>Rdl</i> mutant flight were found, suggesting a role for GABAergic modulation of flight motor programs. Picrotoxin (PTX), a known pro-convulsant that inhibits GABA_A receptors, induced DLM spike patterns that displayed some features, e.g. left-right coordination and ISI⁻¹ range, that could be found in flight or grooming, but distinct from ECS discharges. These quantitative techniques may be employed to reveal overlooked relationships among aberrant motor patterns as well as their links to native motor programs.在果蝇（Drosophila）中，全脑高频电刺激可诱发一套高度刻板的痉挛发作。此类电惊厥发作（electroconvulsive seizures, ECS）表现为神经系统内特征性的尖峰放电活动，且可通过大型间接飞行肌——背纵肌（indirect flight muscles dorsal longitudinal muscles, DLMs）中的惊厥发作全程进行稳定评估，以表征易惊厥突变体的放电特征变化。然而，电惊厥尖峰模式与包括飞行、理毛在内的天然运动程序之间的关联尚未明确，二者的相似性与差异仍有待阐明。我们针对三类运动模式开展了定量尖峰模式分析，具体包括：(1) 总放电频率；(2) 对侧肌纤维间的尖峰时序；(3) 峰间期规律性的短期变异（CV₂）与瞬时放电频率（ISI⁻¹）。这些来自野生型（wild-type, WT）果蝇的基线信息，助力实现了针对三大主要神经递质系统——兴奋性胆碱能（Cha）、抑制性γ-氨基丁酸能（Rdl）以及电性（ShakB）突触传递——的突变效应定量表征。研究结果初步揭示了各类运动模式对不同扰动的易感性差异。我们发现，电惊厥放电的尖峰模式在惊厥阈值、尖峰频率或放电规律性上均存在显著改变。与之形成对比的是，理毛过程未出现明显异常，而Rdl突变体的飞行过程中仅出现小幅但可观测的放电频率降低，这提示γ-氨基丁酸能调制参与了飞行运动程序的调控。印防己毒素（picrotoxin, PTX）作为一种已知的可抑制GABAA受体的致惊厥剂，可诱导背纵肌产生尖峰模式，该模式兼具飞行或理毛时的部分特征（如左右侧协调能力与ISI⁻¹范围），但与电惊厥放电存在显著差异。这些定量分析方法可用于揭示被忽视的异常运动模式间的关联，以及它们与天然运动程序之间的联系。

搜集汇总

背景与挑战

背景概述

该数据集聚焦于果蝇中电惊厥和促惊厥诱导的癫痫放电与原生运动模式（飞行和梳理）的定量比较分析，通过尖峰模式分析揭示不同神经递质系统突变对运动模式的影响。研究发现ECS放电在突变体中表现出显著变化，而梳理行为基本稳定，飞行频率略有下降，同时促惊厥药物诱导的模式与ECS不同但与原生模式有部分相似。数据集支持神经科学和生理学研究，提供基础数据以理解癫痫与运动控制的关系。