FP6Reintegration grant2004–2006

OLFACTORYCIRCUITS · Functional and structural analysis of higher olfactory circuits in Drosophila

FP6 — Marie Curie Actions (Human Resources and Mobility)

Duration
2004-10-01 → 2006-09-30
EU contribution
€80,000
Participants
1
Scheme
IRG

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Results in brief

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.

Data: CORDIS, © European Union

Project objective

My long-term scientific goal is to understand the links between genes and behaviour. For this purpose I use Drosophila as a model system because it is genetically tractable while having a complex behavioural repertoire. My past research at Stanford University focused on the development of highly specific wiring in olfactory circuits. Research supported by the IRG will develop this theme by investigating the functional properties of these circuits. I will develop very high-resolution wiring maps of genetically identified neurons in higher olfactory centres.These will initially be based on high-resolution con-focal microscopy combined with novel image registration techniques. In parallel I will also employ a novel serial block-face scanning electron microscopy technique (SBFSEM), which allows large brain volumes to be reconstructed at up to 10nm resolution. I will then apply state of the art whole cell patch clamp techniques to record the activity of these neurons in intact animals responding to odours. By recording from neurons at successive levels of olfactory processing I hope to understand the integration and transformation of raw sensory information that underlies olfactory perception. Recording from pairs of identified neurons that I predict to be connected by neuro anatomical criteria will be a key part of understanding this information processing.These circuit studies are an essential prerequisite to my long-term goal of understanding the relationship between genes and neural circuits and the relationship between neural circuits and behaviour. Ultimately I hope to gain new insights into the functional properties of the nervous system and how they may be encoded within the genome.

Original text from CORDIS.

Participants

  • THE CHANCELLORS, MASTERS AND SCHOLARS OF THEUNIVERSITY OF CAMBRIDGE · CAMBRIDGECoordinatorCity levelUnknown Region

Links

Data: CORDIS, © European Union