Functional Specialization of Interneuron Dendrites: Identification of Action Potential Initiation Zone in Axonless Olfactory Bulb Granule Cells.

Principal cells in the olfactory bulb (OB), mitral and tufted cells, play key roles in processing and then relaying sensory information to downstream cortical regions. How OB local circuits facilitate odor-specific responses during odor discrimination is not known but involves GABAergic inhibition mediated by axonless granule cells (GCs), the most abundant interneuron in the OB. Most previous work on GCs has focused on defining properties of distal apical dendrites where these interneurons form reciprocal dendrodendritic connections with principal cells. Less is known about the function of the proximal dendritic compartments. In the present study, we identified the likely action potentials (AP) initiation zone by comparing electrophysiological properties of rat (either sex) GCs with apical dendrites severed at different locations. We find that truncated GCs with long apical dendrites had active properties that were indistinguishable from intact GCs, generating full-height APs and short-latency low-threshold Ca2+ spikes. We then confirmed the presumed site of AP and low-threshold Ca2+ spike initiation in the proximal apical dendrite using two-photon Ca2+ photometry and focal TTX application. These results suggest that GCs incorporate two separate pathways for processing synaptic inputs: an already established dendrodendritic input to the distal apical dendrite and a novel pathway in which the cell body integrates proximal synaptic inputs, leading to spike generation in the proximal apical dendrite. Spikes generated by the proximal pathway likely enables GCs to regulate lateral inhibition by defining time windows when lateral inhibition is functional.SIGNIFICANCE STATEMENT The olfactory bulb plays a central role in processing sensory input transduced by receptor neurons. How local circuits in the bulb function to facilitate sensory processing during odor discrimination is not known but appears to involve inhibition mediated by granule cells, axonless GABAergic interneurons. Little is known about the active conductances in granule cells including where action potentials originate. Using a variety of experimental approaches, we find the Na+-based action potentials originate in the proximal apical dendrite, a region targeted by cortical feedback afferents. We also find evidence for high expression of low-voltage activated Ca2+ channels in the same region, intrinsic currents that enable GCs to spike rapidly in response to sensory input during each sniff cycle.