Abstract

Mitral cells express low-voltage activated Cav3.3 channels on their distal apical tuft dendrites (McKay et al., 2006; Johnston and Delaney, 2010). They also discharge Na⁺-dependent dendritic action potentials and release glutamate from these dendrites. Around resting membrane potentials, between −65 and −50 mV, Cav3.x channels are a primary determinant of cytoplasmic [Ca²⁺]. In this study using C57 mice, we present evidence that subthreshold Cav3.x-mediated Ca²⁺ influx modulates action potential evoked transmitter release and directly drives asynchronous release from distal tuft dendrites. Presynaptic hyperpolarization and selective block of Cav3.x channels with Z941 (Tringham et al., 2012) reduce mitral-to-mitral EPSP amplitude, increase the coefficient of variation of EPSPs, and increase paired-pulse ratios, consistent with a reduced probability of transmitter release. Both hyperpolarization and Cav3.x channel blockade reduce steady-state cytoplasmic [Ca²⁺] in the tuft dendrite without reducing action potential evoked Ca²⁺ influx, suggesting that background [Ca²⁺] modulates evoked release. We demonstrate that Cav3.x-mediated Ca²⁺ influx from even one mitral cell at membrane potentials between −65 and −50 mV is sufficient to produce feedback inhibition from periglomerular neurons. Deinactivation of Cav3.x channels by hyperpolarization increases T-type Ca²⁺ influx upon repolarization and increases feedback inhibition to produce subthreshold modulation of the mitral–periglomerular reciprocal circuit.