Because of their characteristic anatomical organization, it has long been suspected that glomeruli are sites of convergence for functionally related olfactory receptor neurons (ORNs). This was supported by classical 2-DG experiments showing that different odors activate different glomeruli. However, the obscure nature of olfactory reception-transduction made it difficult to move beyond this relatively general notion. Progress in the biophysics and molecular biology of olfactory transduction and the discovery of a large, multigene family of putative olfactory receptor genes (ORGs) have revolutionized our thinking about olfactory reception. The mammalian olfactory epithelium is composed of four anatomically distinct zones within which ORNs express ORGs from only one of four subgroups of the multigene family. Within these """"""""expression zones"""""""" individual ORNs that express the same ORGs are randomly dispersed. However, recent findings suggest that axons from ORNs expressing the same ORG converge en route to the bulb and terminate in the same few glomeruli. This implies that glomeruli are sites of convergence for ORNs that """"""""see"""""""" the same molecular sub-domains present on odor molecules. To the extent that this is correct, it follows that the extraction of information about specific odor molecules is the result of neural computation. The initial stage of this computation occurs in glomeruli. ORNs transfer information to the rest of the brain via mitral/tufted cells, the output neurons of the bulb. This transfer is initially regulated by the interneuronal network of the glomerulus. The major premise of this research is that almost nothing is known about the functional organization of glomeruli. Classical anatomical studies have provided some information about the synaptic organization, but very little is known about the functional characteristics of distinct juxtaglomerular (JG) interneuronal cell types, the pharmacology of glomerular synapses, or the dynamics and plasticity of intraglomerular synaptic processing. Interglomerular interactions have long seen suspected, and are theoretically implied by current notions of ORN-glomerular convergence, but rigorous analyses of glomerular interactions are lacking. The major impediment to research on glomeruli is the small size of JG cells, which has rendered them virtually inaccessible to classical physiological approaches. To overcome this obstacle the PI has developed the first mammalian olfactory bulb slice preparation. This preparation is physiologically robust and provides access to the functionally intact microcircuitry of the glomerulus. The PI has already obtained novel insights about functionally distinct JG cell types and synaptic plasticity (LTP). The goal of the proposed research is to use extra- and intracellular and whole-cell perforated-patch recording methods and intracellular labeling to characterize membrane, synaptic, and network mechanisms of glomerular processing and functional interactions among neighboring glomeruli.
