Abnormal Action Potentials Associated with the Shaker Complex Locus of Drosophila

Intracellular recordings of action potentials were made from the cervical giant axon in Shaker (Sh) mutants and normal Drosophila. The mutants showed abnormally long delays in repolarization. The defect is not due to abnormal Ca2+ channels, because it persists in the presence of Co2+, a Ca2+-channel blocker. On the other hand, the K+-channel blocker 4-aminopyridine causes a similar effect in normal animals, suggesting that the Sh mutant may have abnormal K+ conductance. Gene-dosage analysis of Sh shows that the defect is not due to underproduction of an otherwise normal molecule; it may be due to an abnormal molecule produced by the mutated gene. Gel electrophoresis failed to detect an abnormal protein, suggesting that, if Sh codes for a nervous system protein, it is rare. Genetic analysis of the Sh locus indicates three regions. Mutations or chromosome breaks in the two flanking regions cause Sh mutant physiology; the central region shows a "haplolethal effect"--i.e., heterozygous females are lethal

Anatomy of Motor Axons to Direct Flight Muscles in \u3ci\u3eDrosophila\u3c/i\u3e

The direct flight muscles of Drosophila melanogaster are innervated by the anterior dorsal mesothoracic (ADM) nerve and the mesothoracic accessory (MAC) nerve. Each of the four conspicuously large axons in the ADM nerve serves one of the muscles designated pal, pa3, pa4 and pa5. Muscle pa4 is additionally innervated by a very small neurosecretory axon. Muscle pa6, also innervated by the ADM nerve, receives at least one small nerve fibre but no large axon. Muscle pa2 is innervated by a large axon from the MAC nerve. Large motor axons, identified by serial section tracing from their respective muscles, are consistent among different individuals in both relative positions and relative diameters within the ADM nerve

Giant Fibre Activation of Direct Flight Muscles in Drosophila

1. Electrical stimuli delivered to the brain were used to activate the giant fibre of Drosophila. 2. The giant fibre drove a prominent wing opening movement. 3. Intracellular microelectrode recordings from direct wing opener muscle fibres showed that giant fibre activation of an anterior pleural muscle, pa3, was responsible for the wing opening movement. 4. The giant fibre drove a slight wing elevation movement. 5. Intracellular recordings from direct wing elevator muscle fibres showed that these muscles were not activated by the giant fibre. 6. It is suggested that giant fibre-driven wing elevation movements were mediated by the tergotrochanter muscle (TTM)

Drosophila couch potato Mutants Exhibit Complex Neurological Abnormalities Including Epilepsy Phenotypes

RNA-binding proteins play critical roles in regulation of gene expression, and impairment can have severe phenotypic consequences on nervous system function. We report here the discovery of several complex neurological phenotypes associated with mutations of couch potato (cpo), which encodes a Drosophila RNA-binding protein. We show that mutation of cpo leads to bang-sensitive paralysis, seizure susceptibility, and synaptic transmission defects. A new cpo allele called cpo(EG1) was identified on the basis of a bang-sensitive paralytic mutant phenotype in a sensitized genetic background (sda/+). In heteroallelic combinations with other cpo alleles, cpo(EG1) shows an incompletely penetrant bang-sensitive phenotype with ∼30% of flies becoming paralyzed. In response to electroconvulsive shock, heteroallelic combinations with cpo(EG1) exhibit seizure thresholds less than half that of wild-type flies. Finally, cpo flies display several neurocircuit abnormalities in the giant fiber (GF) system. The TTM muscles of cpo mutants exhibit long latency responses coupled with decreased following frequency. DLM muscles in cpo mutants show drastic reductions in following frequency despite exhibiting normal latency relationships. The labile sites appear to be the electrochemical GF-TTMn synapse and the chemical PSI-DLMn synapses. These complex neurological phenotypes of cpo mutants support an important role for cpo in regulating proper nervous system function, including seizure susceptibility

Mutations of the Calcium Channel Gene cacophony Suppress Seizures in Drosophila.

Bang sensitive (BS) Drosophila mutants display characteristic seizure-like phenotypes resembling, in some aspects, those of human seizure disorders such as epilepsy. The BS mutant parabss1, caused by a gain-of-function mutation of the voltage-gated Na+ channel gene, is extremely seizure-sensitive with phenotypes that have proven difficult to ameliorate by anti-epileptic drug feeding or by seizure-suppressor mutation. It has been presented as a model for intractable human epilepsy. Here we show that cacophony (cacTS2), a mutation of the Drosophila presynaptic Ca++ channel α1 subunit gene, is a particularly potent seizure-suppressor mutation, reverting seizure-like phenotypes for parabss1 and other BS mutants. Seizure-like phenotypes for parabss1 may be suppressed by as much as 90% in double mutant combinations with cacTS2. Unexpectedly, we find that parabss1 also reciprocally suppresses cacTS2 seizure-like phenotypes. The cacTS2 mutant displays these seizure-like behaviors and spontaneous high-frequency action potential firing transiently after exposure to high temperature. We find that this seizure-like behavior in cacTS2 is ameliorated by 85% in double mutant combinations with parabss1