Olfactory Coding in the Insect Pheromone Pathway: Models and Experiments

'Much can be learned about complex systems by studying simpler ones. [...] Small systems, and particularly small olfactory systems, seem to use mechanisms and strategies that are not unique to them and we may be better off starting with the modest goal of understanding flies first.' G. Laurent 'Shall we even understand the fly brain?' in 23 Problems in Systems Neuroscience, Oxford University Press, 2006. Our understanding of the computations that take place in the human brain is limited by the extreme complexity of the cortex, and by the difficulty of experimentally recording neural activities, for practical and ethical reasons. Just as the Human Genome Project was preceded by the sequencing of smaller but complete genomes, it is likely that future breakthroughs in neuroscience will result from the study of smaller but complete nervous systems, such as the insect brain. These small nervous systems exhibit general properties that are also present in higher mammals, such as neural synchronization and network oscillations, and we are more likely to understand the role of these phenomena in insects first, before we can apply this knowledge to humans. This project analyzes olfaction, the sense of smell, and uses the moth olfactory brain as a model, because (i) it is relatively simple, (ii) it has been widely described and (iii) it is easily accessible to electrophysiological recordings. Our aim is to understand how sensory information is coded and processed during the detection and processing of odour stimuli, with special emphasis on communication by sexual pheromones. Pheromonal communication constitutes an exceptionally favourable model system for studying olfactory mechanisms, because (i) it is specialized and oriented (emitting females, receiving males), (ii) it involves only a small number of known and available ligands (sexual pheromones) which interact with specific membrane receptors, (iii) the cerebral neural network processing pheromonal information is well delimited and specialized, and (iv) the behavioural response is well characterized. The moth olfactory brain is made of three sets of neurons: (a) the olfactory receptor neurons (ORNs) of the antenna, in large numbers, detect and code the quality (nature of molecules), intensity (number of molecules) and temporal characteristics of the pheromonal signal; (b) the neurons, especially the projection neurons (PNs) of the antennal lobe (AL) in the brain, in smaller numbers, integrate the information delivered by ORNs. All synaptic connections, between ORNs, AL neurons and modulatory neurons from other parts of the brain, take place in a set of ca. 60 glomeruli. In particular, a subset of 2-3 enlarged, sexually dimorphic glomeruli, the macroglomerular complex (MGC), processes the pheromonal information. (c) The Kenyon cells of the mushroom bodies (MBs), in large numbers, process the information received from the PNs. This neural system is of significant scientific and socio-economic interest. Although long neglected, the study of olfaction has considerably expanded over the last fifteen years, stimulated by the interest in its molecular and neural mechanisms as well as the potential applications in many areas. Among the latter are the control of insect populations and 'artificial noses' (a rapidly expanding area of considerable economic importance). The research proposed here will investigate the principles underlying the superior performance of biological olfactory systems and thus will provide the basis for novel developments in these fields.

The aim of our project is to investigate olfactory information processing in the first stages of the olfactory pathway. We will conduct experiments and modelling studies in the pheromone subsystem of the moth Spodoptera littoralis (the cotton leafworm). 1. In experiments we will a) investigate the transduction mechanism in the olfactory receptor neurons (ORNs) with tip-recording in vivo and patch clamp recordings in vitro, b) determine the prevalence and distribution of different types of ORNs and their projections to the macro-glomerular complex (MGC), and c) record the activity of MGC neurons in response to a rich set of odour stimuli while monitoring the local field potential. 2. In modelling we will a) build detailed, biophysical models of the ORNs, combining experimental data (1b) with existing submodels of perireception, reception, and post-reception processes, b) reconstruct the compound signal sent by the ORNs to the MGC based on modelling (2a) and experimental data (1b), c) develop conductance-based models of single glomeruli using modern data fitting technology (synchronization based parameter estimation employing genetic algorithms and multiple shooting) to adjust the models to the data (1b, 1c), d) reduce the detailed models to network models of IF neurons and analyse their response and coding properties mathematically, and e) build similar detailed and reduced models of the full MGC to analyse the following open questions (in both the one-glomerulus and full MGC models): i) Is the connectivity of olfactory systems well described by a random network or does it follow a different construction principle? ii) How does the pheromone system achieve its outstanding sensitivity and specificity and maintain them in the presence of noise? iii) What is the origin and role of oscillations in the MGC or olfactory systems in general? What is the function of phase locking and synchronization and how does inhibition contribute to it?