The Drosophila olfactory system is perhaps one of the most thoroughly investigated neural circuits in terms of its structure and function.  However the mechanisms underlying the specification of different cell types and the construction of the circuit still need to be deciphered.  We believe that a complete understanding of how a simple circuit is constructed and modified to give rise to behavior is a necessary first step in understanding how small circuits are wired up to give rise to a brain.

The antennal lobes are olfactory centers that consist of dense collections of synaptic endings termed glomeruli which are known to be neural substrates for odor coding.  Each glomerulus is composed of synapses between olfactory receptor neurons (ORNs) projection interneurons (PNs) and local interneurons (LNs).  Each glomerulus receives input from ORNs which bear a single odorant receptor, while the LNs integrate information between different glomeruli.  The PNs are believed to carry processed information to the higher centres in the mushroom bodies and lateral horn.  There is evidence for ‘top-down’ information from wide-field serotonergic neurons that terminate within the antennal lobe from the higher centres.  This basic organization is conserved across insect species separated by several million years of evolutionary history and interestingly similar principles are also exploited in mammals. 

In this project, we will study the development of each of the cellular components of the antennal lobe. The adult ORNs develop during pupal life from cells within the antennal imaginal disc and we have some understanding of how cells are specified and are guided to the antennal lobe.  We will further this study and ask which transcription factors specify the different types of ORN cells.  As an entry, we will focus on the empty spiracles (ems) gene the mouse ortholog of which has already been shown to be involved in specification of the olfactory mucosa.  The interneurons (LNs and PNs) arise from neuroblasts within the developing brain; we will establish the origin, lineage and relationship between these two populations of cells.  Both cell types are heterogeneous in terms of their structural patterns, connectivity and neurotransmitter identities.  What are the mechanisms underlying these differences?  We have evidence that ems is one of the determinants of cell identity in central brain neuroblasts.  Does this gene play a role in development of the antennal lobe interneurons in addition?  An attractive model is that cells which share common transcription factor combinations maybe search and lock together during circuit formation.   Testing this idea will require us to study the role of ems in development and re-modeling of dendritic arbors of the interneurons and their ORN counterparts.

The studies proposed above will increase our extant knowledge about the specification of the first level of olfactory circuitry.  Significantly, we believe that it will be possible to use this information and the variety of reagents available in Drosophila in a novel approach to study the olfactory system of the medically important insect species Anopheles.  This insect is a vector to several parasitic diseases and viral infections –malaria, dengue, yellow fever, encephalitis- that result in colossal morbidities in human populations particularly in developing countries.  The major mode of transmission is by the mosquitoes feeding on blood from infected individuals and transferring the disease agent to naïve hosts.  The major strategy for these insects seeking hosts is through olfaction and while our studies will not directly address insect control, it is clear that basic knowledge of olfactory system development could have a potential impact on design of control agents in later studies.