Abstract

Hypersynchronous neural activity is a characteristic feature of seizures. Although many Drosophila mutants of epilepsy-related genes display clear behavioral spasms and motor unit hyperexcitability, field potential measurements of aberrant hypersynchronous activity across brain regions during seizures have yet to be described. Here, we report a straightforward method to observe local field potentials (LFPs) from the Drosophila brain to monitor ensemble neural activity during seizures in behaving tethered flies. High frequency stimulation across the brain reliably triggers a stereotypic sequence of electroconvulsive seizure (ECS) spike discharges readily detectable in the dorsal longitudinal muscle (DLM) and coupled with behavioral spasms. During seizure episodes, the LFP signal displayed characteristic large-amplitude oscillations with a stereotypic temporal correlation to DLM flight muscle spiking. ECS-related LFP events were clearly distinct from rest- and flight-associated LFP patterns. We further characterized the LFP activity during different types of seizures originating from genetic and pharmacological manipulations. In the ‘bang-sensitive’ sodium channel mutant bangsenseless (bss), the LFP pattern was prolonged, and the temporal correlation between LFP oscillations and DLM discharges was altered. Following administration of the pro-convulsant GABA_A blocker picrotoxin, we uncovered a qualitatively different LFP activity pattern, which consisted of a slow (1-Hz), repetitive, waveform, closely coupled with DLM bursting and behavioral spasms. Our approach to record brain LFPs presents an initial framework for electrophysiological analysis of the complex brain-wide activity patterns in the large collection of Drosophila excitability mutants.

摘要

超同步神经活动是癫痫发作的一个特征。尽管癫痫相关基因的许多果蝇突变体表现出明显的行为痉挛和运动单位过度兴奋，但尚未描述癫痫发作期间跨大脑区域异常超同步活动的场电位测量。在这里，我们报告了一种直接的方法来观察果蝇的局部场电位 (LFP )大脑在行为系留的果蝇癫痫发作期间监测整体神经活动。大脑中的高频刺激可靠地触发电惊厥发作 (ECS) 尖峰放电的刻板序列，在背纵肌 (DLM) 中很容易检测到，并伴有行为痉挛。在癫痫发作期间，LFP 信号显示出特征性的大振幅振荡，与 DLM 飞行肌肉尖峰具有刻板的时间相关性。ECS 相关的 LFP 事件与休息和飞行相关的 LFP 模式明显不同。我们进一步表征了源自遗传和药理学操作的不同类型癫痫发作期间的 LFP 活动。在“爆炸敏感”钠通道突变体bangsenseless ( bss), LFP 模式延长, LFP 振荡和 DLM 放电之间的时间相关性发生改变。在施用促惊厥剂 GABA _A阻滞剂印防己毒素后，我们发现了一种性质不同的 LFP 活动模式，其中包括缓慢 (1-Hz)、重复的波形，与 DLM 爆发和行为痉挛密切相关。我们记录大脑 LFPs 的方法为大量果蝇兴奋性突变体中复杂的全脑活动模式的电生理分析提供了一个初始框架。