In order to better understand locomotor recovery in Drosophila melanogaster, and to test our hypothesis that the aforementioned genes pertaining to the cAMP “memory cascade” play a role in locomotor adaptation, we examined the influence of several genes on motor recovery by observing how their loss of function mutants react and adapt to middle-leg amputation, while taking into account the established notion of wild type locomotor recovery. This was carried out using the FlyWalker system in order to study the kinematic adaptations, which occur after amputation in Canton-S (wild type) Drosophila melanogaster flies. We focused on the spatial parameters as these better reflect the kinematic improvements observed during neurorehabilitation.
Our data showed for the first time that Drosophila can recover from an injury and most strikingly, that the same genes that control olfactory associative learning also control motor learning, which per se will have a strong impact in the scientific community. Accordingly, we included additional aims in this project.
After the positive results of locomotor adaptation that occur post middle-leg amputation in various Drosophila melanogaster wild type lines including Canton-S, we sought to test if this phenotype was reproducible in the evolutionarily distant Drosophila species Drosophila pseudoobscura and Drosophila repleta. With this experiment, we aimed to understand whether there is any evolutionary conservation of our behavioral readout, which, in case of a positive result, adds robustness of our genetic model for neurorehabilitation.
Overall, the data regarding amputated walking behavior on Drosophila pseudoobscura and repleta strongly suggest that these, like their Canton-S Drosophila melanogaster counterpart, can efficiently deal with the amputation of both middle legs, doing so by adapting various locomotor parameters which grants them the ability to walk using only four legs.
Another physiological factor that seems affect the motor recovery is the aging. Results suggested that with aging the long-term memory is affected, whilst the short-memory is maintained. Our results demonstrated the effect of normal senescence in the normal walking pattern. Accordingly, it was verified the kinematic changes caused by the aging, such as the reduction of average speed. The most important evidence retired from these quantifications was the huge similarity between 1 and 7-weeks-old flies, suggesting that the level of learning acquired in 1-weeks-old flies is equivalent to the level of unlearning in 7-weeks-old flies.
In all age stages, the amputation procedure induced an immediate decrease of locomotor activity, as well as decrease of the instantaneous speed. Thus, it’s clearly that flies can readjust their motor representation in order to adapt to new biomechanical challenge.
Here I describe a novel approach to unravel an old and important question in the field of neuroscience, a strong case should be presented for publication in a high impact journal (currently under preparation). The acquired data indeed support the initial hypothesis of this project. Thus, the impact becomes reinforced since the initial hypothesis became fully supported. Finally, none of the current results precludes the executions of the initial aims, quite the opposite; it reinforces the validity and interest of those aims, which will be carried out in the short-term.
During the period of my MSCA I have participated in several dissemination activities. These included scientific meetings with my peers and with the general public. Equally important was my interaction with undergraduate medical students and master students from our institute, where I shared my results and scientific interest but also I fostered critical thinking and the importance of scientific research to solve the most complex biomedical questions facing our society.
