Schematic illustrating how excitation of mitral cells by CCK released from tufted cell terminals in the inner plexiform layer (IPL) might provide a critical link in a reciprocal excitatory synaptic pathway between two isofunctional glomeruli receiving inputs from the same olfactory receptor (OR). The OR inputs excite principal neurons (superficial tufted cells and mitral cells) of both glomeruli. Action potentials of superficial tufted cells of one glomerulus propagate through the IPL to the opposite side of the bulb, where they trigger release of CCK from the tufted cell terminals. The CCK migrates by extrasynaptic diffusion (RED arrows) to nearby mitral cells linked to the opposite mirror symmetric glomerulus. Mitral cells are excited by CCK, and relay this excitation to their sister superficial tufted cells by intraglomerular transmission between apical dendritic tufts (GREEN arrow). The sister tufted cells send CCK-ergic projections back to excite mitral cells linked to the opposing glomerulus. Mitral cell spikes are relayed as bulbar output to olfactory cortex (OC). This positive feedback loop may operate on slow modulatory time scales to amplify output from pairs of glomeruli connected by the intrabulbar association system. Not shown are putative glutamatergic excitatory synapses of superficial tufted cell terminals onto granule cells, which may coordinate activity of isofunctional glomeruli on faster (sniff-to-sniff) time scales. The gain of the interglomerular amplifier depends on the effectiveness of excitation by diffusional signaling (RED arrows), and might be adjustable by varying the spatial dispersion of IPL terminals through activity-dependent plasticity. Often used olfactory receptors and glomeruli responding to frequently encountered odorants are predicted have higher gain, due to efficient CCK signaling from compact IPL terminal fields. Seldom used glomeruli that only respond to rarely encountered odorants are predicted to have lower gain, due to inefficient CCK signaling from dispersed IPL terminal fields. Abbreviations: EPL, external plexiform layer; GL, glomerular layer; IPL, inner plexiform layer.