Cellular Communication in the Adult and Developing Olfactory System.

Communication between the cells that make up the olfactory system is critical both for the ability of the system to detect and identify chemical information in the environment and for the ability of those neurons to find appropriate paths and make functional connections within the developing olfactory system. We focus on three different systems: the role of Nitric Oxide in the adult olfactory system, the role of serotonin in the adult olfactory system, and the role of cell adhesion molecules and Eph/ephrin interactions in the developing olfactory system. We take advantage of insect model systems including Manduca sexta and Drosophila melanogaster to investigate these processes.

Nitric Oxide in the Olfactory System

Almost all organisms that possess an olfactory system exhibit a similar organization in their primary olfactory neuropil. Olfactory receptor neurons (ORNs) that detect volatile molecules in the periphery extend axons into the brain where they form networks and communicate with local interneurons (LNs) and projection neurons (PNs) in roughly spheroidal neuropil called glomeruli. Understanding the way in which odor information is processed, as well as the plasticity inherent in that processing, requires an understanding of the communication between the ORNs, LNs and PNs within and among olfactory glomeruli. While there has been considerable progress in describing the roles of synaptic communication involving conventional chemical neurotransmitters in the olfactory system, the function of gaseous neurotransmitters such as nitric oxide (NO) is much less understood. We have three projects that investigate NO in olfactory processing:

Project 1: Characterize odor-induced NO production and diffusion within the AL using optical recordings of both calcium and nitric oxide responses.Project 2: Characterize the functional roles of NO signaling in AL neurons using invivo and in-vitro electrophysiology. Project 3: Characterize the behavioral consequences of interfering with NO signaling in the AL using established olfactory based behavioral assays.

Serotonin as a Neuromodulator in the Olfactory System

The responsiveness of the olfactory system can change depending on the physiological state of the animal. Serotonin (5-HT) functions as both a neurotransmitter and a neuromodulator and is especially important as a neuromodulator in the olfactory system. To better characterize the effects of 5-HT in the Manduca sexta olfactory system, and to better describe the different types of interneurons that process information in the olfactory system, we are characterizing the four different receptors that respond to serotonin. Our central hypothesis is that different 5HT receptors are expressed by different cellular elements of the AL which allows for modulation of the specific tasks of these neuronal cell types. This allows the coordinated manipulation of individual circuit elements to enhance salient features of olfactory stimuli resulting in enhanced performance in olfactory-guided behaviors. We are testing these ideas through three projects:

Project 1: Characterize the distributions, pharmacological profiles and target ion conductances of 5HT receptors in the ALs. Project 2: Determine the contribution of each 5HT receptor subtype to the overall effects of 5HT on the glomerular network properties. Project 3: Determine the behavioral consequences of 5HT receptor activation within the AL.

Appropriate axon pathfinding is critical to proper development of the olfactory system. This is especially true in the olfactory system where all of the ORNs that express a particular receptor are thought be randomly distributed in the periphery yet manage to all coalesce at the appropriate glomerulus in the antennal lobe. In collaboration with Leslie Tolbert's laboratory, we are examining the role of Eph receptor/ephrin signaling as well as other molecules using RNAi to knockdown the expression of these mRNAs and examining the effects of these manipulations on the proper axon targeting in the olfactory system.