title: Presynaptic T-type Ca2+ channels modulate dendrodendritic mitral-mitral and mitral-periglomerular connections in mouse olfactory bulb.
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 [Ca(2+)]. In this study using C57 mice, we present evidence that subthreshold Cav3.x-mediated Ca(2+) 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 [Ca(2+)] in the tuft dendrite without reducing action potential evoked Ca(2+) influx, suggesting that background [Ca(2+)] modulates evoked release. We demonstrate that Cav3.x-mediated Ca(2+) 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 Ca(2+) influx upon repolarization and increases feedback inhibition to produce subthreshold modulation of the mitral-periglomerular reciprocal circuit.
authors.affiliation: Department of Biology, University of Victoria, Victoria, British Columbia, V8W 2Y2, Canada, Program in Neurosciences and Mental Health, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto, Ontario, M5G 1X8, Canada, and.
authors.forename: Adam
authors.initials: A
authors.lastname: Fekete
authors.affiliation: Department of Biology, University of Victoria, Victoria, British Columbia, V8W 2Y2, Canada, Sussex Neuroscience, School of Life Sciences, University of Sussex, Falmer, Brighton, BN1 9QG, United Kingdom.
authors.forename: Jamie
authors.initials: J
authors.lastname: Johnston
authors.affiliation: Department of Biology, University of Victoria, Victoria, British Columbia, V8W 2Y2, Canada, kdelaney@uvic.ca.
authors.forename: Kerry R
authors.initials: KR
authors.lastname: Delaney
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D020747:Calcium Channels, T-Type / Q000502:physiology*; D051244:Caveolin 3 / Q000502:physiology*; D003712:Dendrites / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005260:Female; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009433:Neural Inhibition / Q000502:physiology; D009830:Olfactory Bulb / Q000502:physiology*; D009833:Olfactory Pathways / Q000502:physiology*; D009924:Organ Culture Techniques; D017729:Presynaptic Terminals / Q000502:physiology*
chemical_list: D020747:Calcium Channels, T-Type; C495548:Cav3 protein, mouse; D051244:Caveolin 3
keywords: T-channel (Cav3); asynchronous release; basal Ca2+ level; dendrodendritic release; olfactory mitral cells; subthreshold potential