Multiple Conductances Cooperatively Regulate Spontaneous Bursting in Mouse Olfactory Bulb External Tufted Cells

Abstract

External tufted (ET) cells are juxtaglomerular neurons that spontaneously generate bursts of action potentials, which persist when fast synaptic transmission is blocked. The intrinsic mechanism of this autonomous bursting is unknown. We identified a set of voltage-dependent conductances that cooperatively regulate spontaneous bursting: hyperpolarization-activated inward current (I_h), persistent Na⁺ current (I_NaP), low-voltage-activated calcium current (I_L/T) mediated by T- and/or L-type Ca²⁺ channels, and large-conductance Ca²⁺-dependent K⁺ current (I_BK). I_h is important in setting membrane potential and depolarizes the cell toward the threshold of I_NaP and I_T/L, which are essential to generate the depolarizing envelope that is crowned by a burst of action potentials. Action potentials depolarize the membrane and induce Ca²⁺ influx via high-voltage-activated Ca²⁺ channels (I_HVA). The combined depolarization and increased intracellular Ca²⁺ activates I_BK, which terminates the burst by hyperpolarizing the membrane. Hyperpolarization activates I_h and the cycle is regenerated. A novel finding is the role of L-type Ca²⁺ channels in autonomous ET cells bursting. A second novel feature is the role of BK channels, which regulate burst duration. I_L and I_BK may go hand-in-hand, the slow inactivation of I_L requiring I_BK-dependent hyperpolarization to deactivate inward conductances and terminate the burst. ET cells receive monosynaptic olfactory nerve input and drive the major inhibitory interneurons of the glomerular circuit. Modulation of the conductances identified here can regulate burst frequency, duration, and spikes per burst in ET cells and thus significantly shape the impact of glomerular circuits on mitral and tufted cells, the output channels of the olfactory bulb.