Modulation of olfactory processing in the Drosophila larva
Final Report Abstract
Our mood and internal state strongly affect how we act and react when exposed to certain stimuli or situations. The same stimulus can evoke a very different behavioral outcome just depending on how we feel. Everybody knows that it is a bad idea to go shopping when one is hungry - we would just buy more and higher caloric items than normally. How can internal state exert such a strong influence on our behavior? Environmental stimuli - e.g. supermarket items - stay the same, but somehow our brain must process this information differently. To elucidate the detailed underlying neural mechanisms of this phenomenon, I turned to the olfactory system of the fruit fly larvae. Larvae show distinct behaviors towards olfactory stimuli, such as avoidance and attraction. I could now show that their behavior is also statedependent; an odor that is aversive for fed larvae turns out to become attractive once larvae are food deprived for a few hours. We already have a very good idea about the neural architecture underlying the first olfactory processing center of the larva based on EM reconstruction data. This wiring diagram revealed that there is a diversity of interneurons, neuromodulatory neurons and projection neurons in the larval antennal lobe, suggesting that this center is not just a simple information relay center to the higher brain. Indeed, I found that within the larval antennal lobe, a network of local inhibitory neurons and projection neurons is modulated by synaptic and extra synaptic release of serotonin from CSD, a prominent serotonergic neuron with previously unknown function. Food deprivation evokes a combination of changes in glutamatergic inhibitory circuits and serotonergic excitation onto projection neurons. And surprisingly, different projection neuron types drive innate aversive and attractive behaviors and project to different higher brain regions. My results demonstrate how neuromodulatory circuits in early sensory processing can shape olfactory valence by selecting appropriate antennal lobe output pathways depending on internal state. Such circuit motif allows flexible switching between behavioral outputs on top of hardwired neural connectivity. Both neuronal architecture and molecular mechanisms in the Drosophila olfactory system are strikingly similar to those in mammals, making this model useful to understand conserved principles of neuromodulation in olfactory processing and behavior.
