We are investigating the neural circuit basis of olfactory perception in Drosophila. Olfactory information enters the fly brain in 50 glomeruli of the antennal lobe. Second order neurons then project to two structures, the mushroom body, which is required for olfactory learning but apparently dispensable for innate olfactory behaviour, and the lateral horn. We have previously demonstrated that olfactory input to the lateral horn is spatially stereotyped across individuals and that pheromone and general odours are mapped to different zones. We hypothesise that this poorly characterised brain centre is where odour information starts to be transformed into behaviourally relevant representations.
Pheromones: One initial focus has been on the processing of the pheromone signal cVA, a male pheromone that is repulsive for other males but a female aphrodisiac. We have recently shown striking anatomical dimorphisms in the dendrites of third order lateral horn neurons that appear to receive cVA information from incoming projection neuron axons. Two small groups of neurons show male specific overlap while a third shows overlap in females. We have used in vivo patch clamp to record the activity of neurons in both sexes, finding that one group, aSP-f neurons, show pheromone responses only in males, while a second group, aSP-g neurons, show responses only in females. This circuit layout has the logic of a developmental circuit switch, in which a common input is mapped onto one of two possible outputs.
Integration: cVA is repulsive for males. What do they find attractive? Volatile fly pheromones of female origin have been long sought but remain elusive. However Richard Benton’s group has demonstrated that a specific food derived compound, PAA, can act as a male aphrodisiac. Intriguingly, we have shown in collaboration that unlike other food signals PAA information projects to the pheromone processing centre of the lateral horn. It is therefore likely that third order neurons in this area integrate information about food and fly odours that regulate fly courtship.
General Odours: Besides pheromone processing, we are also interested in higher processing of other odours of strong innate significance. At some point we imagine that the representation of odours of different behavioural significance will start to converge. Although the lateral horn likely subserves some of this function, initial results suggest that this transformation/integration must continue in lateral horn target areas.
Learned and Innate Behaviour: The majority of our work is focussed on innate odour responses. However, flies can of course learn to associate odours with reward or punishment. This then raises the question of how a learned responses can interact with (and perhaps suppress) an innate response. What is/are the circuit locus/i of this interaction? Is it mediated by dendritic integration of classical chemical synaptic inputs? Or does it depend on other mechanisms?
Connectomics: One major new approach to understanding the circuit basis of behaviour is the use of connectomics. As part of an international collaboration, we are mapping the olfactory and memory circuits using a whole brain electron microscopy dataset, originally obtained by Davi Bock. We work closely with the Drosophila Connectomics Group based in the Zoology department (and directed by Greg), to leverage connectomics results to drive our experimental work.
Methods: All of our circuit analysis work is supported by significant efforts in the development of experimental and analytic tools for circuit mapping, for which we are quite well known. In addition we have adapted a wide variety of approaches developed by others for our specific experimental needs. Please see the resources section for further details.