Activation of Granule Cell Interneurons by Two Divergent Local Circuit Pathways in the Rat Olfactory Bulb.

The olfactory bulb (OB) serves as a relay region for sensory information transduced by receptor neurons in the nose and ultimately routed to a variety of cortical areas. Despite the highly structured organization of the sensory inputs to the OB, even simple monomolecular odors activate large regions of the OB comprising many glomerular modules defined by afferents from different receptor neuron subtypes. OB principal cells receive their primary excitatory input from only one glomerular channel defined by inputs from one class of olfactory receptor neurons. By contrast, interneurons, such as GABAergic granule cells (GCs), integrate across multiple channels through dendodendritic inputs on their distal apical dendrites. Through their inhibitory synaptic actions, GCs appear to modulate principal cell firing to enhance olfactory discrimination, although how GCs contribute to olfactory function is not well understood. In this study, we identify a second synaptic pathway by which principal cells in the rat (both sexes) OB excite GCs by evoking potent nondepressing EPSPs (termed large-amplitude, nondendrodendritic [LANDD] EPSPs). LANDD EPSPs show little depression in response to tetanic stimulation and, therefore, can be distinguished other EPSPs that target GCs. LANDD EPSPs can be evoked by both focal stimulation near GC proximal dendrites and by activating sensory inputs in the glomerular layer in truncated GCs lacking dendrodendritic inputs. Using computational simulations, we show that LANDD EPSPs more reliably encode the duration of principal cell discharges than DD EPSPs, enabling GCs to compare contrasting versions of odor-driven activity patterns.SIGNIFICANCE STATEMENT The olfactory bulb plays a critical role in transforming broad sensory input patterns into odor-selective population responses. How this occurs is not well understood, but the local bulbar interneurons appear to be centrally involved in the process. Granule cells, the most common interneuron in the olfactory bulb, are known to broadly integrate sensory input through specialized synapses on their distal dendrites. Here we describe a second class of local excitatory inputs to granule cells that are more powerful than distal inputs and fail to depress with repeated stimulation. This second, proximal pathway allows bulbar interneurons to assay divergent versions of the same sensory input pattern.