Glial expression of Drosophila UBE3A causes spontaneous seizures that can be modulated by 5-HT signaling.

Misexpression of the E3 ubiquitin ligase gene UBE3A is thought to contribute to a range of neurological disorders. In the context of Dup15q syndrome, additional genomic copies of UBE3A give rise to the autism, muscle hypotonia and spontaneous seizures characteristics of the disorder. In a Drosophila model of Dup 15q syndrome, it was recently shown that glial-driven expression of the UBE3A ortholog dube3a led to a "bang-sensitive" phenotype, where mechanical shock triggers convulsions, suggesting glial dube3a expression contributes to hyperexcitability in flies.

Glial expression of causes spontaneous seizures modulated by 5-HT signaling.

Misexpression of the E3 ubiquitin ligase is thought to contribute to a range of neurological disorders. In the context of Dup15q syndrome, excess genomic copies of is thought to contribute to the autism, muscle tone and spontaneous seizures characteristic of the disorder. In a model of Dup 15q syndrome, it was recently shown glial-driven expression of the ortholog led to a "bang-sensitive" phenotype, where mechanical shock triggers convulsions, suggesting glial expression contributes to hyperexcitability in flies.

Intense light unleashes male-male courtship behaviour in wild-type .

courtship studies have elucidated several principles of the neurogenetic organization of complex behaviour. Through an integration across sensory modalities, males perform stereotypic patterns of chasing, courtship song production and copulation attempts. Here we report a serendipitous finding that intense light not only enhances courtship toward female targets but also triggers unexpected courtship behaviours among male flies.

carrying epilepsy-associated variants in the vitamin B6 metabolism gene display allele- and diet-dependent phenotypes.

Pyridox(am)ine 5 -phosphate oxidase (PNPO) catalyzes the rate-limiting step in the synthesis of pyridoxal 5 -phosphate (PLP), the active form of vitamin B6 required for the synthesis of neurotransmitters gamma-aminobutyric acid (GABA) and the monoamines. Pathogenic variants in have been increasingly identified in patients with neonatal epileptic encephalopathy and early-onset epilepsy. These patients often exhibit different types of seizures and variable comorbidities.

Distinct Aging-Vulnerable and -Resilient Trajectories of Specific Motor Circuit Functions in Oxidation- and Temperature-Stressed .

In , molecular pathways affecting longevity have been extensively studied. However, corresponding neurophysiological changes underlying aging-related functional and behavioral deteriorations remain to be fully explored. We examined different motor circuits in across the life span and uncovered distinctive age-resilient and age-vulnerable trajectories in their established functional properties.

Fly seizure EEG: field potential activity in the brain.

Hypersynchronous neural activity is a characteristic feature of seizures. Although many 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 brain to monitor ensemble neural activity during seizures in behaving tethered flies.

Differential effects on neuromuscular physiology between loss-of-function mutation and paraquat-induced oxidative stress in .

Oxidative stress is thought to be a major contributor to aging processes. Here, we report differential effects on neurotransmission caused by loss-of-function mutations of () and by paraquat (PQ) feeding in . We demonstrated alterations in mutants; the larval neuromuscular junction displayed supernumerary discharges and the adult giant-fiber escape pathway showed increased latency and poor response to repetitive high-frequency stimulation.

Pyridox (am) ine 5'-phosphate oxidase deficiency induces seizures in Drosophila melanogaster.

Pyridox (am) ine 5'-phosphate oxidase (PNPO) is a rate-limiting enzyme in converting dietary vitamin B6 (VB6) to pyridoxal 5'-phosphate (PLP), the biologically active form of VB6 and involved in the synthesis of neurotransmitters including γ-aminobutyric acid (GABA), dopamine, and serotonin. In humans, PNPO mutations have been increasingly identified in neonatal epileptic encephalopathy and more recently also in early-onset epilepsy. Till now, little is known about the neurobiological mechanisms underlying PNPO-deficiency-induced seizures due to the lack of animal models.

Milk-whey diet substantially suppresses seizure-like phenotypes of , a voltage-gated sodium channel mutant.

The mutant harbors a dominant, gain-of-function allele of the voltage-gated sodium channel gene, (). The mutant flies display severe seizure-like phenotypes, including neuronal hyperexcitability, spontaneous spasms, ether-induced leg shaking, and heat-induced convulsions. We unexpectedly found that two distinct food recipes used routinely in the research community result in a striking difference in severity of the phenotypes.

Distinctions among electroconvulsion- and proconvulsant-induced seizure discharges and native motor patterns during flight and grooming: quantitative spike pattern analysis in flight muscles.

In , 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.

Two novel forms of ERG oscillation in Drosophila: age and activity dependence.

Over an animal's lifespan, neuronal circuits and systems often decline in an inherently heterogeneous fashion. To compare the age-dependent progression of changes in visual behavior with alterations in retinal physiology, we examined phototaxis and electroretinograms (ERGs) in a wild-type D. melanogaster strain (Canton-S) across their lifespan.

Lithium-Responsive Seizure-Like Hyperexcitability Is Caused by a Mutation in the Voltage-Gated Sodium Channel Gene .

() is an X-linked dominant mutation in identified more than 40 years ago. A previous study showed that caused spontaneous tremors and defects in reactive climbing behavior, and that these phenotypes were significantly suppressed when mutants were fed food containing lithium, a mood stabilizer used in the treatment of bipolar disorder (Williamson, 1982). This unique observation suggested that the mutation affects genes involved in lithium-responsive neurobiological processes.

Mutation of orthologous prickle genes causes a similar epilepsy syndrome in flies and humans.

Objective: Genetically tractable fruit flies have been used for decades to study seizure disorders. However, there is a paucity of data specifically correlating fly and human seizure phenotypes. We have previously shown that mutation of orthologous PRICKLE genes from flies to humans produce seizures.

Flight and seizure motor patterns in Drosophila mutants: simultaneous acoustic and electrophysiological recordings of wing beats and flight muscle activity.

Abstract Tethered flies allow studies of biomechanics and electrophysiology of flight control. We performed microelectrode recordings of spikes in an indirect flight muscle (the dorsal longitudinal muscle, DLMa) coupled with acoustic analysis of wing beat frequency (WBF) via microphone signals. Simultaneous electrophysiological recording of direct and indirect flight muscles has been technically challenging; however, the WBF is thought to reflect in a one-to-one relationship with spiking activity in a subset of direct flight muscles, including muscle m1b.

prickle modulates microtubule polarity and axonal transport to ameliorate seizures in flies.

Recent analyses in flies, mice, zebrafish, and humans showed that mutations in prickle orthologs result in epileptic phenotypes, although the mechanism responsible for generating the seizures was unknown. Here, we show that Prickle organizes microtubule polarity and affects their growth dynamics in axons of Drosophila neurons, which in turn influences both anterograde and retrograde vesicle transport. We also show that enhancement of the anterograde transport mechanism is the cause of the seizure phenotype in flies, which can be suppressed by reducing the level of either of two Kinesin motor proteins responsible for anterograde vesicle transport.

Automated quantification of locomotion, social interaction, and mate preference in Drosophila mutants.

Automated tracking methods facilitate screening for and characterization of abnormal locomotion or more complex behaviors in Drosophila. We developed the Iowa Fly Locomotion and Interaction Tracker (IowaFLI Tracker), a MATLAB-based video analysis system, to identify and track multiple flies in a small arena. We report altered motor activity in the K(+) and Na(+) channel mutants, Hk(1) and para(ts1), which had previously been shown to display abnormal larval locomotion.

Post-eclosion odor experience modifies olfactory receptor neuron coding in Drosophila.

Olfactory responses of Drosophila undergo pronounced changes after eclosion. The flies develop attraction to odors to which they are exposed and aversion to other odors. Behavioral adaptation is correlated with changes in the firing pattern of olfactory receptor neurons (ORNs).