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The what and where of operant self-learning mechanisms in Drosophila
AuthorJulien Colomb, Ezequiel Mendoza, Diana Pauly, Sathishkumar Raja, Björn Brembs
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DescriptionIn most operant learning experiments, two biological processes take place, world-learning (the process assigning value to sensory stimuli) and self-learning (the process assigning value to a specific action or movement). Using tethered Drosophila at the torque meter, the two processes can be separated and studied independently. Manipulation of synaptic plasticity via the cAMP pathway disrupts world-learning but does not affect self-learning. Conversely, inhibiting PKC activity affects self-learning, but leaves world-learning intact. In order to decipher the molecular bases of self-learning, we use the genetic tools available in Drosophila in combination with behavioral tests. Because the expression of an inhibitor of PKC interferes with self-learning, we have started to screen the available non-lethal mutants of the different PKC isoforms for deficits in self-learning. Interestingly, self-learning of the tested mutants was unaffected. In order to overcome potential compensatory mechanisms among the different PKC isoforms during development, we are now using an RNAi-induced downregulation of specific PKC isoforms only during adulthood (via the Pswitch system) to test their role in self-learning. In addition to PKC, we also investigate the involvement of the fly orthologue of the human FOXP2 gene. Both a P-Element insertion and RNAi-mediated knockdown of the last exon of the Drosophila FoxP gene did not lead to alterations of the gross brain anatomy, nor to an impairment in operant world-learning. However, both fly strains were impaired in operant self-learning. These results suggest a specific involvement of the Drosophila FoxP gene in the neural plasticity underlying operant self-learning but not other forms of learning. To investigate the effects of RNAi knockdown and P-Element insertion on FoxP abundance and localization in the fly central nervous system, we have initiated an analysis of FoxP expression patterns on the mRNA as well as on the protein level.
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