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Functional and structural analysis of higher olfactory circuits in Drosophila

Final Activity Report Summary - OLFACTORYCIRCUITS (Functional and structural analysis of higher olfactory circuits in Drosophila)

I have developed a major new 3D atlas of higher olfactory centres in the fruit fly by combining genetic single neuron labelling and computational neuroanatomy. This revealed a number of organisational principles including a spatial division between pheromone and fruit odours in one of the two higher olfactory centres of the fly, the lateral horn. This work was the first major quantitative study of input and output of the lateral horn down to single cell resolution. To give one example at this level, we observed that there are both inhibitory and excitatory inputs carrying information about a specific male pheromone to a sexually dimorphic region of the lateral horn. We examined their projections in detail and identified a class of lateral horn output neuron that is likely to receive this information - we are testing this functionally. These results reinforce the hypothesis that the lateral horn may be critical for translating odour information into behavioural responses.

In the meantime I also learnt the new technique of in vivo whole cell patch physiology, which allowed me to record from single genetically labelled neurons in a live fly. We recorded from to two populations of higher olfactory neurons of the lateral horn. One class turned out not to be odour responsive - they may in fact be modulatory neurons. The second class was indeed odour responsive; we are continuing to characterise how many different kinds of odours they respond to and how their responses change with odour concentration.

IRG support was for the first 2 years in a longer project (3 years in the first instance). In the third year of the project, in addition to the projects above, I also worked on the application of a new electron microscope technique, 3D serial block face scanning electron microscopy (SBFSEM), to the fly olfactory system. This will allow very high-resolution images of large fractions of the fly brain so that it will be possible to trace which neurons are connected. We obtained promising data for some fly brain samples when I visited the microscope's developers in Heidelberg. However the genetic technique designed to pick out small groups of neurons in this electron microscope images did not perform as expected so we are currently optimising this.