title: Altered synaptic transmission at olfactory and vomeronasal nerve terminals in mice lacking N-type calcium channel Cav2.2.
abstract: We investigated the role of voltage-activated calcium (Cav) channels for synaptic transmission at mouse olfactory and vomeronasal nerve terminals at the first synapse of the main and accessory olfactory pathways, respectively. We provided evidence for a central role of the N-type Cav channel subunit Cav2.2 in presynaptic transmitter release at these synapses. Striking Cav2.2 immunoreactivity was localised to the glomerular neuropil of the main olfactory bulb (MOB) and accessory olfactory bulb (AOB), and co-localised with presynaptic molecules such as bassoon. Voltage-clamp recordings of sensory nerve-evoked, excitatory postsynaptic currents (EPSCs) in mitral/tufted (M/T) and superficial tufted cells of the MOB and mitral cells of the AOB, in combination with established subtype-specific Cav channel toxins, indicated a predominant role of N-type channels in transmitter release at these synapses, whereas L-type, P/Q-type, and R-type channels had either no or only relatively minor contributions. In Cacna1b mutant mice lacking the Cav2.2 (α1B) subunit of N-type channels, olfactory nerve-evoked M/T cell EPSCs were not reduced but became blocker-resistant, thus indicating a major reorganisation and compensation of Cav channel subunits as a result of the Cav2.2 deletion at this synapse. Cav2.2-deficient mice also revealed that Cav2.2 was critically required for paired-pulse depression of olfactory nerve-evoked EPSCs in M/T cells of the MOB, and they demonstrated an essential requirement for Cav2.2 in vomeronasal nerve-evoked EPSCs of AOB mitral cells. Thus, Cacna1b loss-of-function mutations are unlikely to cause general anosmia but Cacna1b emerges as a strong candidate in the search for mutations causing altered olfactory perception, such as changes in general olfactory sensitivity and altered social responses to chemostimuli.
authors.affiliation: Department of Physiology, University of Saarland School of Medicine, Kirrbergerstrasse, Building 58, D-66421, Homburg, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Weiss
authors.forename: Martina
authors.initials: M
authors.lastname: Pyrski
authors.forename: Petra
authors.initials: P
authors.lastname: Weissgerber
authors.forename: Frank
authors.initials: F
authors.lastname: Zufall
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000378:metabolism; D020864:Calcium Channels, N-Type / Q000235:genetics / Q000378:metabolism*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005260:Female; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009830:Olfactory Bulb / Q000187:drug effects / Q000502:physiology*; D051842:Olfactory Marker Protein / Q000378:metabolism; D009832:Olfactory Nerve / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D046509:Tissue Culture Techniques; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D050599:Vesicular Glutamate Transport Protein 2 / Q000378:metabolism; D019147:Vomeronasal Organ / Q000187:drug effects / Q000294:innervation / Q000502:physiology*
chemical_list: C498441:Bsn protein, mouse; C500963:Cacna1b protein, mouse; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D020864:Calcium Channels, N-Type; D009419:Nerve Tissue Proteins; D051842:Olfactory Marker Protein; C497598:Omp protein, mouse; C493477:Slc17a6 protein, mouse; D050599:Vesicular Glutamate Transport Protein 2; D014446:Tyrosine 3-Monooxygenase
keywords: Cacna1b; aggression; channelopathy; olfactory plasticity; ω-conotoxin GVIA