There is a drastic increase in DLM firing frequency in eas1 mutants following electroconvulsive seizures (ECS). The temporal characteristics of the ECS-induced wing buzzing shows a gross discrepancy with the DLM firing pattern. Unlike in wild-type, the wing beat frequency in these mutants does not appear to be temporally coupled with the DLM firing episode. Instead, an abrupt termination of wing beats occurs during DLM firing, followed by quiescence prior to a second bout of wing beats when DLM firing is terminated.
Injection of 25mM valproate saline solution greatly increases the seizure threshold of eas1 mutants (i.e. suppresses the seizure phenotype), although this is still below wild-type levels.
Rapid acute exposure to 100% CO[], N[] or He causes seizure-like activity in eas1 mutants. Seizure-like activity is characterized by violent spinning of the flies accompanied by rapid uncoordinated movement of the wings, legs and abdomen. The initial bout of seizure-like activity, which usually occurs within 10 seconds of the onset of gas exposure, is followed by a period of paralysis in which the flies lay motionless. The paralysis is interrupted by bouts of delayed seizure-like activity that begins 30 to 60 seconds following the initial seizure-like activity. The delayed seizure-like activity is much more variable than the initial activity, as it often consists of multiple bouts of activity interspersed with periods of paralysis.
Repeat exposure to CO[] reduced the severity of seizure-like activity. eas1 flies that are exposed to a second round of CO[] exposure as soon as they recover from an initial acute exposure to CO[], a process that takes approximately 3 minutes, are immobilized by the exposure but the amount of seizure-like activity is reduced. For example, following the first exposure, 83% of bss1 flies display delayed seizure-like activity while following the second exposure only 58% of the flies display this activity.
Exposure of eas1 flies to a 50/50 mix of CO[] and O[] results in initial and delayed seizure-like activity, indicating that hypercapnia is sufficient to trigger seizure-like activity in these flies as they have more than twice the level of atmospheric oxygen during exposure to the 50/50 mix. These flies are also susceptible to CO[] induced anesthetization.
Mixtures of 95% N[] and 5% O[] or 95% He and 5% O[] do not trigger seizure-like activity in eas1 flies. In fact, at 98% N[] or He and 2% O[], these flies do not exhibit seizure-like activity, although they do become sluggish. When the amount of O[] is reduced even further to 1% or less, the flies begin to become anesthetized and in many cases exhibit seizure-like activity.
Exposure of eas1 to pure CO[], He or O[] for 2-5 minutes results in initial seizure-like activity but fails to generate the delayed seizure-like activity seen following acute exposure. After the initial seizure-like activity, the flies remain motionless throughout the duration of the 2- to 5-minute gas exposure. Once the gas exposure ends, the flies gradually recover normal function without displaying any delayed seizure-like activity.
The giant fiber(GF)-dorsal longitudinal indirect flight muscle (DLM) neuronal circuit is more sensitive to seizure induction in mutants than in wild-type flies; seizures can be induced with high-frequency brain stimulation of shorter or less intensity in the mutant animals. The mutant animals show predominantly type II seizures, although type I seizures are also commonly observed.
The seizure threshold following short wavetrains of high-frequency electrical stimuli (0.5ms pulses at 200Hz for 300ms) is reduced in mutant flies (3.4 +/- 0.5 V) compared to controls.
The threshold for activation of the giant fiber in mutant animals following single stimulus pulses (0.2ms duration, 0.5Hz) is not significantly different from that of wild type.
Bang sensitive paralytic mutant.
Brief paralysis following exposure to mechanical shock; this phenotype suppressed by mlenap-ts1 mutation at its permissive temperature; release of neurotransmitter at larval neuromuscular junction is apparently normal.