parats1 homozygous adults exhibit fully penetrant paralysis 120sec after being shifted to 38[o]C temperature.
No paralysis is seen in parats1/+ mutant flies in response to elevated temperatures.
When reared continuously at 22[o]C, neuromuscular junction size increases at a constant rate in mutant larvae, as occurs in wild type. However, when the are shifted to 29[o]C, NMJ size remains constant in the mutants, in contrast to the increase in size seen in wild type.
parats1 mutants suppress temperature-induced synaptic outgrowth.
In controls, high K[+] stimulation results in the formation of "ghost boutons" - boutons containing synaptic vesicles but lacking active zones and presynaptic structures. But blocking action potentials in neurons by shifting parats1 larvae to restrictive temperatures prevents this.
parats1/Y males and parats1/para60 females are significantly more sensitive to isoflurane than control flies; the latency between nerve shock and excitatory junctional potential onset at the neuromuscular junction treated is significantly larger in the mutant flies than in controls following treatment with isoflurane.
parats1 flies are completely paralysed at 38[o]C.
parats1 homozygotes are viable but exhibit paralysis following heat shock. parats1/paraJS1 flies are also viable but do not exhibit paralysis following heat shock.
Neither parats1 nor parats1/parats115 flies show a significantly shortened lifespan. However, the brains of these flies show neurodegeneration. parats1 flies become instantly paralyzed upon exposure to a 3 minute 38oC heat shock, but recover instantly when transferred to 22oC.
parats1 flies are hypersensitive to isoflurane; isoflurane increases the delay from the stimulus to the onset of synaptic currents in both wild-type and mutant flies but the delay in response to isoflurane is increased in mutant axons compared to controls.
sesB1/parats1 double mutants display no significant paralysis after heat shock (90s, 30[o]C) and vortexing (10s).
Atpα2206/parats1 double mutants display no significant paralysis after heat shock (90s, 30[o]C) and vortexing (10s).
parats1 mutants paralyse within seconds of exposure to 38o.
parats1 mutant flies show flaccid paralysis when exposed to 300C for 2 minutes.
Mutant flies show a rapid onset of paralysis when placed at 38oC.
Like wild-type larvae, parats1 mutants exhibit an increase in quantal content and enhanced locomotor activity when moved from a food slurry environment at 18oC to an agar plate at 22oC. When the temperature is shifted to 34oC for 20 minutes and maintained at 29oC after this, parats1 larvae become paralysed, while wild-type larvae continue to show enhanced locomotion. After two hours of paralysis, quantal content levels of the parats1 mutants drop to those seen at 18oC on the food slurry, while wild-type quantal content (following two hours of enhanced activity) is higher than at 22oC. During the two hours at 29oC, wild-type larvae show an increase in the number of large subsynaptic eIF-4E aggregates, while the amount of aggregates remain unchanged in the parats1 mutants.
Injection of 5-HT or norepinephrine increases the heart rate in parats1 mutant flies at 30oC, and the change in rate is no different from that seen in wild-type controls. Injection of acetylcholine does no result in a significant change in heart rate in parats1 mutant flies at 30oC (in contrast to wild-type controls which show an increase in heart rate when injected with acetylcholine). Injection of dopamine or octopamine increases the heart rate in parats1 mutant flies at 30oC, but the increase is significantly less than that seen in wild-type controls.
Spike-like potentials are seen when local field potential (LFP) recordings are made from the differential activity between one electrode place in between the mushroom bodies at approximately the level of the base of the calyces versus one placed in the lamina or medulla of the optic lobes. These spike-like potentials are significantly suppressed in parats1 in flies subjected to heat shock at 38oC for 30 seconds, but are normal in flies kept at 25oC.
Life span at 28oC is essentially the same as wild-type controls.
Mutant flies are paralysed at 27oC.
parats1 flies treated with sodium valproate (NaVP) do not show a reduction in body weight, in contrast to wild-type flies. Treatment of parats1 flies with NaVP causes an increase in mortality as is seen in wild-type flies.
The production of wing abnormalities induced by valproate in wild-type flies is suppressed by the parats1 mutation.
Flies are sensitive to ether (lower concentrations are required for anaesthesia compared to wild-type flies).
Shows no temperature sensitive ERG on/off transients mutant phenotype.
The difference in courtship song interpulse interval between parats1 and wild-type males shows a significant positive correlation with temperature, while the difference in courtship song amplitude between parats1 and wild-type males shows a significant negative correlation with temperature.
Homozygous flies show significant resistance to dichloro-diphenyl-trichloro ethane (DDT) compared to wild-type flies.
Temperature sensitive block or decrease is synaptic transmission at the neuromuscular junctions. Embryos shifted to restrictive temperature of 32oC at 12hr AEL and kept at this temperature for the remainder of embryogenesis show no spontaneous movement nor were their tracheae inflated. Muscle pattern formation and shortening of the ventral nerve cord (VNC) is normal. Glutamate receptor clusters are found at the extrajunctional region, these are not seen in wild type embryos. Embryos reared at 30oC show a few clusters at the extrajunctional region and some at the synaptic site. These embryos show low spontaneous movement and few hatch. At 25oC receptors in the extrajunctional region disappear and are localised at te synaptic site. Embryos develop and hatch normally. 10hr heat shock at 34oC after 12hr AEL causes receptor accumulation at the extrajunctional region. The number of receptor clusters increases at higher temperatures. Neural activity is required for receptor accumulation.
Temperature sensitive paralysis threshold is 32oC. Flies become paralysed within 15 seconds of a temperature shift to 39oC and recover completely within 15 seconds of shifting back to room temperature.
Sub-anaesthetic concentration of carbon dioxide enhances the paralytic phenotype.
Mutation has no effect on larval heartbeat at temperatures between 20oC and 37.5oC.
Homozygous larvae raised at the restrictive temperature (37oC for 6 hours/day from late embryogenesis through to third larval instar) do not show an increased frequency of ectopic neuromuscular synapses, but do show an increased frequency of ectopic neuromuscular synapses if the larvae are also mutant for tipEunspecified. Embryos raised at 34oC show an increased frequency of immature filopodial contacts on muscle fibres 6 and 7 ("collateral sprouts") compared to wild-type embryos raised at 34oC.
Homozygotes show increased sensitivity to halothane, chloroform and trichloroethylene in an inebriometer assay (an assay of geotactic and postural behaviour) compared to wild-type flies. Decapitated flies lose the halothane sensitive phenotype.
The delivery of an electrical buzz (50-400 msec) to the brain has no significant effect on parats1 mutant flies.
Adults are reversibly paralysed at 29oC, at this temperature nerve conduction at the neuromuscular junction (NMJ) appears to be completely blocked. parats1/Df(1)D34 transheterozygotes die as first instar larvae. Homozygous embryos maintain periodic bursting activity with an excitatory junction current (EJC) amplitude similar to wild type, but bursting frequency and EJCs per burst are significantly reduced. Embryos hatch at 30oC but show a dramatic reduction in hatching efficiency at 32oC. Nerve conduction at the embryonic NMJ is reduced at 30oC, nearly suppressed at 32oC and blocked at 34oC. Embryos reared at 34oC for 8 hours from the onset of synaptogenesis exhibit distribution of glutamate receptors on the muscle, not localised at the NMJ. A shift in temperature mid-synaptogenesis does not affect receptor clustering at the NMJ. Synaptic morphology, at the light microscope level, of embryonic NMJs raised at the restrictive temperature is not significantly different from wild type. These hypoactive synapses occupy a smaller area of the muscle surface relative to wild type causing increased synaptic density (the branch and bouton numbers are not altered).
parats1 mlenap-ts1 double mutant bristle sensory cells in small-patch mosaic flies have normal branching and terminal arborisation patterns in the central nervous system.
Double mutants with mlenap-ts1 or parats1 show no exaggeration of the paralytic phenotypes, nor any efect on their viability and fertility. These results suggest stmA does not interact with para or mle.
Flies become paralysed at 29oC.
Flies become paralysed at 29-31oC. The long-latency response of the dorsal longitudinal muscle disappears abruptly as the temperature is increased to 31 +/- 1oC, although the short-latency response is normal.
The temperature at which mutant flies become paralysed is dependent on the rearing temperature; flies raised at a low temperature (8oC) become paralysed at a lower temperature than flies raised at a high (30oC) temperature. Temperatures up to 7oC above the paralytic temperature usually do not block the dorsal longitudinal muscle response to giant fibre stimulation. The jump muscle response is variable at this high temperature, some flies have a normal response, some have no response at all, and some have a reduced amplitude response. The interval from brain stimulation of the giant fibre to a response in the DLM or jump muscle is longer than in wild-type flies at all temperatures. Both the DLM and the jump muscle have a weaker following frequency than wild-type, which can be rescued by injecting 4-aminopyridine into mutant flies.
Reversible paralysis at 25oC.
Dissociated central nervous system cultures from parats1 larvae appear morphologically normal and cells have a similar survival rate to wild-type at both 22oC and at the restrictive temperature of 35oC. parats1 cell cultures show a significantly higher resistance to veratridine than wild-type cells at 22oC, although the resistance is not as high as for mlenap-ts1 cells. At 35oC, the resistance of parats1 cells to veratridine increases to a level similar to mlenap-ts1 cells.
Homozygous or hemizygous adults show normal walking and flying ability at 22oC to 25oC, but at higher temperatures become increasingly debilitated, and become completely paralysed in less than 5 seconds when shifted to 29oC. This paralysis is reversible; mobility is recovered in less than 2 seconds when paralysed flies are shifted back to 22oC. Paralysis and recovery can be induced repeatedly in the same individuals with no apparent harm. Although paralysis is initially complete at 29oC, some recovery of movement is seen in flies kept at 29oC, and after 30 minutes at 29oC, flies can right themselves and have limited walking ability. Larval mobility is unaffected.
Marked reduction in number of embryonic neurons in cell culture expressing sodium currents in these alleles (O'Dowd et al., 1987; O'Dowd et al., 1989). temperature-sensitive