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.

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.

In Drosophila, 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 (Cha), inhibitory GABAergic (Rdl) and electrical (ShakB) 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 Rdl 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.

In Drosophila, 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 (Cha), inhibitory GABAergic (Rdl) and electrical (ShakB) 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 Rdl 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.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.