Neural circuit basis of olfactory perception in Drosophila

The brain is a network of interconnected neurons; information processing depends on exactly which neurons are connected and the strength and sign of these connections. A major goal of neuroscience is to understand the principles governing information processing in order to understand how human and animal brains think in health and disease.
Our goal is to understand how smell turns into behaviour. The sensory neurons that detect smells are connected to brain areas that trigger behaviours or form memories by only one level of processing; this is much more direct than vision.
We are studying how smell is processed in fruit fly brains. Although their brains are smaller and simpler, there are many organisational similarities to vertebrates. One key advantage is that we can use genetics to identify the same neurons in the brains of different experimental animals. We have developed strategies to record electrically from identified neurons as flies smell different odours. We are also developing wiring diagrams that describe how neurons are connected at successive levels of processing and how this differs between the sexes. By combining this information we hope to understand the transition from sensation to action in this small brain.

The long-term motivation of our work is to understand how neural circuits process sensory information and transform this into behaviour. We are particularly interested in behaviours that are encoded in the genome through the specification of the development and function of neural circuits. We use the olfactory system of the fruit fly as a model system.
Our strategy is to combine high-resolution neuroanatomy down to the level of single identified neurons with targeted in vivo neurophysiology and behavioural analysis. Olfactory receptor neurons project axons to form a highly stereotyped olfactory map in the first olfactory centre in the brain, the antennal lobe. Second order neurons, called projection neurons, relay this information to two higher olfactory centres, the lateral horn and the mushroom body. The mushroom body is required for olfactory learning but apparently dispensable for innate olfactory behaviour. We are therefore focussing our efforts on the lateral horn. We hypothesise that this poorly characterised brain centre is where odour information starts to be transformed into a representation appropriate to instruct behaviour.
Using genetic cell labelling and image registration to combine data from multiple brains, we have produced a comprehensive map of sex differences in the wiring of the fly brain. We identified sexually dimorphic higher order olfactory neurons that are likely to underlie sex-specific olfactory behaviour. Detailed analysis defined a novel circuit element, a bidirectional circuit switch in the brain, for the first time in any animal. This switch re-routes pheromone information between two target neuron populations and may underlie sex-specific behavioural response to pheromones.
Ongoing work includes complementary investigations of general odour processing in the lateral horn, where we find neurons with a huge range of tuning properties. The lab also continues to develop new technologies in support of our scientific questions, that should be of widespread utility. These include methods for ultra-rapid tissue labelling along with computational tools to map and compare neuronal structures.
Future work will dissect the developmental basis and behavioural significance of the sexually dimorphic switch we have identified. We will also follow the processing of non-pheromone odours that appear to have substantial innate odour significance. We will study behavioural and neuronal integration of coincident positive stimuli (such as food and pheromone) and stimuli of opposite valence. We will also investigate the relationship between learned and innate odour responses. Finally we will continue our work in genetic and computational methods development.