The development and function of neural circuits

All animals are born with a number of innate behaviours which form the basis for each species` responses to stimuli from the environment. However, most innate behaviours are plastic, meaning that individuals can adapt their behaviour to their specific surroundings. Together with Nikolaas Tinbergen in Oxford and Karl von Frisch in Munich, Konrad Lorenz conducted pioneering research on instinctive behaviours. For this ground-breaking work, the three researchers were awarded the Nobel Prize in Physiology or Medicine in 1973. Tinbergen posed four now- famous questions about innate behaviours: What happens inside the organism (causation)? How does a behaviour develop in the organism (ontogeny)? How does the behaviour contribute to the species` survival or reproduction (function)? And finally, why did this behaviour arise in the species in question (evolution)? Tinbergen, Lorenz and von Frisch dealt with the questions of function and evolution. The objective of our research is to address the causation and ontogeny of behaviours. For this purpose, we will use the Drosophila melanogaster fruit fly as a model. In order to investigate causation, we have chosen the sexual behaviour of the male fruit fly. Soon after they are born, males already begin performing a complicated courtship ritual when they encounter a receptive female. They sing and dance for the female before they ultimately copulate. Naturally, only the males exhibit this behaviour. We recently succeeded in identifying the neural networks which control this behaviour in the male`s brain. Astonishingly, the same networks are found in the brains of female fruit flies. At present, we do not know what function these neurons perform in the female or how they differ from those of males. These questions will be important focuses in our future research. In the development of the fruit fly, mating behaviour is clearly genetically programmed, as adult flies can begin the courtship ritual practically immediately after emerging from the puparium. Instinctively, the males play the male role and the females play the female role. We were recently able to demonstrate that this difference is mainly attributable to a single gene which is known as "fruitless" and is formed in all of the neural networks involved. Fruitless exists in two forms: an active form in males and an inactive form in females. If a male is modified in such a way that only the female form of the gene is created, the male will no longer show any interest in females. If, on the other hand, a female develops the male form of the gene, she will behave like a normal male and start flirting with other females. The proteins generated by the fruitless gene are transcription factors, meaning that fruitless controls how other genes are expressed and thus controls behaviour. We are currently working to identify these genes and to find out how they program this typical male mating behaviour in the fly`s brain. Another important aspect in the development of innate behaviours is the "wiring" of the nervous system. In order for a fly to perform a behaviour properly, more than 100,000 neurons must be linked to each other correctly. In this context, each neuron has to find out which other cell it has to form a connection with. In our early efforts and in our current work, we found a number of molecules which can control the formation of neural networks. For example, we are now beginning to understand how the right and left halves of the nervous system are connected and how photoreceptors in the fly`s eye and olfactory neurons in its antenna find their target neurons in the brain and are thus able to form a network.

Recent advances in light microscopy have provided biologists with the possibility of observing and manipulating cellular processes in intact living organisms at unprecedented spatial and temporal resolution. These methods are having a particularly dramatic impact in the neurosciences and in developmental and cell biology. The IMP is strong in all of these areas, with my own group focusing on the functional analysis of neural circuits in Drosophila. The award of the Wittgenstein Prize provided a unique opportunity to invest in equipment and personnel that would expand our capacity and skills in advanced light microscopy, ensuring that we and other researchers at the IMP could remain at the cutting edge of these developments. To this end, the Wittgenstein Prize was used to purchase an advanced multiphoton confocal microscope, and components required for the in house construction of various optical systems. Moreover, the funds supported the recruitment of an optical physicist, Dr. Katrin Heinze, to a 5-year staff scientist position at the IMP, as well as various coworkers using these methods in specific research projects. The major technical or biological accomplishments of this research have been (1) the establishment of an optogenetic system for Drosophila, (2) the establishment of an optical tracking system for studies of Drosophila locomotion, (3) imaging of neuronal activity in the Drosophila central nervous system, (4) imaging of sound-evoked activity in the mouse auditory cortex, and (5) analysis of photounbinding of protein complexes.