The long-term goals of this research are to understand better the operation of a simple cortical circuit, the olfactory bulb. This knowledge will improve understanding of the mechanisms of olfactory discrimination, potentially important in some olfactory dysfunctions; and will contribute to understanding of cortex function in general.
The specific aims i nvolve tests of spatial extent and synaptic mechanisms for lateral inhibition between cells associated with regions of the bulb (glomeruli) that receive input from different types of olfactory sensory neurons. This input appears to create a spatial map of odors across the surface of the olfactory bulb. Lateral inhibition, by increasing contrast between weakly and strongly activated regions of the bulb, should therefore increase the brain's ability to distinguish between small differences in the location of activity within that map. One form of lateral inhibition between output neurons of the bulb is mediated by granule interneurons and is reasonably well understood. Another set of lateral connections, via periglomerular (PG) interneurons using GABA and dopamine as transmitters is thought to be inhibitory but is poorly understood. The spatial extent of these lateral influences and the mechanisms of PG cell action are investigated here. The electrical activity of neurons in thin slices of olfactory bulb maintained in vitro will be recorded using patch-clamp electrodes, in response to stimulation of individual glomeruli. Neurotransmitter mechanisms will be investigated using bath-applied drugs that stimulate or block transmitter action. Results of the recordings in main and accessory olfactory bulbs slices will be simulated in computer models to make testable predictions about the function of the intact systems.
