Blocking of Dendrodendritic Inhibition Unleashes Widely Spread Lateral Propagation of Odor-evoked Activity in the Mouse Olfactory Bulb

The olfactory circuitry in mice involves a well-characterized, vertical receptor type-specific organization, but the localized inhibitory effect from granule cells on action potentials that propagate laterally in secondary dendrites of mitral cell remains open to debate. To understand the functional dynamics of the lateral (horizontal) circuits, we analyzed odor-induced signaling using transgenic mice expressing a genetically encoded Ca2+ indicator specifically in mitral/tufted and some juxtaglomerular cells. Optical imaging of the dorsal olfactory bulb (dOB) revealed specific patterns of glomerular activation in response to odor presentation or direct electric stimulation of the olfactory nerve (ON). Application of a mixture of ionotropic and metabotropic glutamate receptor antagonists onto the exposed dOB completely abolished the responses to direct stimulation of the ON as well as discrete odor-evoked glomerular responses patterns, while a spatially more widespread response component increased and expanded into previously nonresponsive regions. To test whether the widespread odor response component represented signal propagation along mitral cell secondary dendrites, an NMDA receptor antagonist alone was applied to the dOB and was found to also increase and expand odor-evoked response patterns. Finally, with dOB excitatory synaptic transmission completely blocked, application of 1 mM muscimol (a GABAA receptor agonist) to a circumscribed volume in the deep external plexiform layer (EPL) induced an odor non-responsive area. These results indicate that odor stimulation can activate olfactory reciprocal synapses and control lateral interactions among olfactory glomerular modules along a wide range of mitral cell secondary dendrites by modulating the inhibitory effect from granule cells.