Atypical PKC and persistent FoxP expression are key molecular components of operant self-learning, a form of motor learning, in Drosophila motor neurons

Motor learning is not only a key invention of the many new animals evolving new body plans during the Cambrian, it is also central to human existence such as in learning to speak or walk, rehabilitation after injury, or sports. Evidence suggests that all forms of motor learning may share an evolutionary conserved molecular plasticity pathway. Here we present novel insights into the molecular processes underlying a kind of motor learning in the fruit fly Drosophila, operant self-learning. We have discovered that the Forkhead Box gene FoxP is not required in the fly brain for this type of learning. Instead, atypical protein kinase C (aPKC) appears to be a central component in a plasticity process that takes place in FoxP-expressing motor neurons in the ventral nerve cord. Using CRISPR/Cas9 to knock out canonical aPKC interaction partners bazooka and the kidney and brain gene (KIBRA) in adult animals, we found that aPKC likely acts via non-canonical pathways in this form of learning. We also found that 14 but not 7 days after CRISPR/Cas9-mediated knockout of FoxP in adult animals, learning is impaired, suggesting that adult FoxP expression is required for operant self-learning.