What is the function of FoxP in operant self-learning?

• Applicant: Professor Dr. Björn Brembs
• Subject Area: Cognitive, Systems and Behavioural Neurobiology
• Term: from 2017 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 376818398

The Forkhead Box P2 (FOXP2) transcription factor is the first gene discovered to be specifically involved in the development of speech and language. Recent studies in birds, mice and fruit flies have shown that the gene exerts this involvement via its conserved function in a particular form of operant conditioning: operant self-learning. In operant self-learning, the subject learns about the outcomes of its own behavior and modifies the behavior accordingly. The neurobiology underlying this recently described form of learning is largely unknown, only Protein Kinase C and the FoxP gene family have been identified across taxa to be critically involved. The mechanism underlying operant self-learning has also been shown not to underlie other forms of learning, such as operant world-learning, allowing for a very rigorous behavioral analysis of the specificity of any of our neurobiological manipulations. In this application, we propose a combination of highly specific, validated genetic and biochemical tools and rigorous behavioral physiology, to identify and characterize the FoxP expressing neurons and circuits involved in operant self-learning in the fruit fly Drosophila. To this end, we will generate transgenic fly lines with which we will manipulate not only the expression of FoxP generally, but also the activity of FoxP expressing neurons. We will also generate monoclonal antibodies against the FoxP protein not only to study endogenous FoxP expression patterns, but also to validate and characterize our manipulations of FoxP expression. Behavioral experiments will then provide the information about which manipulation of FoxP expression in which neurons or the activation/inactivation of which neurons had a specific effect on operant self-learning (and not operant world-learning). The results of this research in the fruit fly will provide us with mechanistic insights into a novel form of behavioral learning (operant self-learning) which is one of the essential neurobiological underpinnings of speech and language acquisition in humans. As this form of learning is associated not only with speech and language disorders, but also with psychiatric disorders such as substance abuse, Tourette's or compulsive disorders, as well as with dyspraxias more broadly, the basic science on operant self-learning is instructive for clinical research in these areas as well. In fact, operant self-learning is being researched as one treatment option for stroke patients, with the aim to increase their mobility.

• DFG Programme: Research Grants