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. By putting this information together 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. We have selected olfaction because it is a very shallow sensory system as few as 2 synapses separate the sensory neurons from brain structures involved in memory and behaviour. Drosophila is a very attractive model because of the unique combination of molecular genetics, favourable scale and complexity and (recently) electrophysiological accessibility.|Our strategy is to combine high-resolution neuroanatomy down to the level of single identified neurons with targeted in vivo neurophysiology. 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.|Our mapping efforts will involve the use of genetic single cell labelling and image registration to combine data from multiple brains, an approach we have recently used to provide the first detailed description of the olfactory input to the lateral horn. We will also test and pursue higher resolution optical and electron microscopy techniques that will allow us to identify synaptically coupled neurons.|We will study odour coding by developing methods to present many odour stimuli to flies. We will record activity by targeted whole cell patch clamp of genetically labelled cell types. This technique gives a very high-resolution view of the spiking and subthreshold activity of individual neurons. We will complement this approach with the use of multiphoton calcium imaging to study more neurons simultaneously (with lower resolution of their activity).|We will also study the interaction between presynaptic projection neurons and postsynaptic neurons of the lateral horn by the use of paired recordings or photostimulation of defined projection neurons.|These experiments will help us to understand the principles of information transfer and transformation at a key stage of the olfactory pathway and more generally the mechanism by which raw sensory information is processed into appropriate behavioural responses.