The superficial tufted and mitral cell output neurons of the mouse olfactory bulb have dual roles in insulin sensing

Abstract

The olfactory bulb (OB) contains multiple, parallel projection neurons to relay the nature of a stimulus. In a mouse ex vivo slice preparation, we used patch-clamp electrophysiology to measure intrinsic properties, excitability, action potential (AP) shape, voltage-activated conductances, and neuromodulation in the newly-categorized superficial tufted cells (sTCs) compared with those of mitral cells (MCs). We propose that a marked difference in voltage-dependent current represents distinct ion channel populations that affect the kinetics of action potentials, and evokes an increase in sTC firing frequency, albeit both types of projection neurons having similar AP spiking activity. Triple-colored immunofluorescence and RNA scope were used to detect co-localization of the Kv1.3 ion channel and the insulin receptor in sTCs, with [~]73% of sTCs expressing both. The sTCs were modulated by bath application of insulin - increasing AP firing frequency by 97%, attributable to an 8% decrease in the intraburst interval, and a reduction of the latency to first spike by 37%. We conclude that there may be a range of neuromodulators of sTCs that may alter excitability and fine-tune olfactory information processing or metabolic balance. SUMMARY STATEMENTSuperficial tufted cells, as output neurons of the olfactory bulb, were electrophysiologically studied to be insulin sensitive. Brain insulin signaling represents a manner in which olfactory and metabolic circuitry are intertwined.