Spatial Structure of Synchronized Inhibition in the Olfactory Bulb

Olfactory sensory input is detected by receptor neurons in the nose, which then send information to the olfactory bulb (OB), the first brain region for processing olfactory information. Within the OB, many local circuit interneurons, including axonless granule cells, function to facilitate fine odor discrimination. How interneurons interact with principal cells to affect bulbar processing is not known, but the mechanism is likely to be different from that in sensory cortical regions because the OB lacks an obvious topographical organization. Neighboring glomerular columns, representing inputs from different receptor neuron subtypes, typically have different odor tuning. Determining the spatial scale over which interneurons such as granule cells can affect principal cells is a critical step toward understanding how the OB operates. We addressed this question by assaying inhibitory synchrony using intracellular recordings from pairs of principal cells with different intersomatic spacing. We found, in acute rat OB slices from both sexes, that inhibitory synchrony is evident in the spontaneous synaptic input in mitral cells (MCs) separated up to 220 μm (300 μm with elevated K⁺). At all intersomatic spacing assayed, inhibitory synchrony was dependent on Na⁺ channels, suggesting that action potentials in granule cells function to coordinate GABA release at relatively distant dendrodendritic synapses formed throughout the dendritic arbor. Our results suggest that individual granule cells are able to influence relatively large groups of MCs and tufted cells belonging to clusters of at least 15 glomerular modules, providing a potential mechanism to integrate signals reflecting a wide variety of odorants.

SIGNIFICANCE STATEMENT Inhibitory circuits in the olfactory bulb (OB) play a major role in odor processing, especially during fine odor discrimination. However, how inhibitory networks enhance olfactory function, and over what spatial scale they operate, is not known. Interneurons are potentially able to function on both a highly localized, synapse-specific level and on a larger, spatial scale that encompasses many different glomerular channels. Although recent indirect evidence has suggested a relatively localized functional role for most inhibition in the OB, in the present study, we used paired intracellular recordings to demonstrate directly that inhibitory local circuits operate over large spatial scales by using fast action potentials to link GABA release at many different synaptic contacts formed with principal cells.