Research

Drosophila Fragile X model

Drosophila Fmr1 ortholog (dfmr1), has 35% identity and 60% similarity with its’s human pair and better part of identical gene sequence is relevant for fragile X syndrome (FXS). Drosophila Fragile X (FX) model is usually created with either point mutations or deletions of all- or majority of- the dfmr1 gene-coding region. This gen is greatly expresses in the central nervous system and it is essential for synaptic plasticity therefore has impact on great number of neuronal processes important for behavior in Drosophila.

Phenotypes represented in Drosophila FX model have large degree of similarity with pathological symptoms presented in FX patients. For instance, FX flies have uncoordinated locomotor behavior measured by climbing or flight assays that corresponds with delayed motor development in some FX patients. The same is with FX Drosophila and humane patient’s impaired learning and memory. Furthermore, even neurological changes in flies corresponds to those in FX patients.

FX Drosophila represent various behavioral and other changes including changes in:

Social interaction in Drosophila Fragile X model

FX mutation in Drosophila affects courtship behavior. In this kind of fly courtship is always the same ritual consisting of few phases culminating in successful copulation. Percentage of time spent in this ritual measured by courtship assay is significantly abbreviated in FX flies.

Another type of behavior changed in FX Drosophila compared to the wild type (WT) is grooming. Grooming in WT Drosophila is short lasting but become seriously increased in FX Drosophila. It is interesting grooming time in mutant flies increase with age. Having in mind that grooming is measure of repetitive behavior we can determine one more similarity between mutant flies and FX patients known to exhibit repetitive behavior.

Learning and memory in Drosophila Fragile X model

Tests for assessing learning and memory in Drosophila are usually either based on avoidance conditioning paradigm or conditioned courtship paradigm. In the first case flies are introduced with two odors. First odor is followed with electrical shock, and the second odor is introduced without the shock. During this “training” flies are supposed to learn to avoid odor flowed with the shock. They are than tested in T-maze to check if they learned to pair the correct odor with the shock. FX flies were more choosing T-maze chambre with shock linked odor than the WT and failed to retain what they’ve learned after 2 minutes and one day showing defects in immediate recall and long-term memory respectively.

Test conducted immediately after training and one hour after training showed that Fragile X flies forgot what they have learnt and were trying to copulate as much as controls that were not trained. This study first discovered defects in immediate recall memory, memory that lasts 0–2 minute after training, and short-term memory that lasts out to one hour after training in FX Drosophila. Long term memory of training can be examined with test based on courtship paradigm. Test entitles 7 hours of continuous training and is performed after 4 days flies spent in isolation. Using this test Banerjee et al. proved that long term memory of the training is impaired in dfrm1 mutants.

In conditioned courtship paradigm during training Drosophila male is paired with unreceptive female for an hour. WT Drosophila usually learns that it’s attempts for copulation will fail and courtship is reduced 40% or more in the final 10 minutes compared to the first 10 minutes of that hour. In old, 20 days age, FX Drosophila this learning during training is reduced compared to the WT but is normal in young Drosophila indicating cognitive decline with age. In the next step males are paired with receptive female and if their memory is good, because of earlier failed attempts, they should be less interesting for copulation compared with males that weren’t trained before. Test is performed 2 minutes, one hour, 2-7 hours and one day after training to assess respectively immediate recall memory (earlier referred as learning), short term memory, medium term memory and long-term memory. Young FX Drosophila flies that had satisfying learning during training are showing defects in immediate recall, short term and long-term memory.

Circadian Rhythms in Drosophila Fragile X model

Circadian rhythm behavior is set by the light dark cycle of the day and is displayed in the most species including Drosophila and of course humans. Molecular clock that run circadian rhythm is so precise that in Drosophila circadian behavior is maintained even if flies are in constant dark for a few weeks. This means that Drosophilas kept in total darkness will be active during their common day time and relatively inactive in the night. FX mutants are capable to maintain almost normal circadian behavior when regular shifts of light and dark are present but unlike WT, FX Drosophila fail to preserve this behavior in total darkness.

Sleep in Drosophila Fragile X model

One study demonstrate that FX Drosophila has prolonged sleep due to extend sleeping episodes. This pattern is present in normal light day shifts and preserved in conditions of total darkness. FX Drosophila also defer from the WT in the matter of recovery of sleep deprivation. After a period of sleep deprivation WT flies sleep longer, while FX flies don’t possess such recovery mechanism.

Adult climbing

Climbing abilities naturally decline with age in WT Drosophila, but this decline is dramatically enhanced in FX Drosophila reaching minimal climbing rate at 25 day post eclosion and older days.

Crawling behavior in larva Drosophila Fragile X model

Drosophila Fragile X model has significantly deferent crawling pattern than the WT. Namely, mutants have less linear crawling with more shifts in motion (with angle higher than 20°).

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