title: Inhibition [corrected] of olfactory receptor neuron input to olfactory bulb glomeruli mediated by suppression of presynaptic calcium influx.
abstract: We investigated the cellular mechanism underlying presynaptic regulation of olfactory receptor neuron (ORN) input to the mouse olfactory bulb using optical-imaging techniques that selectively report activity in the ORN presynaptic terminal. First, we loaded ORNs with calcium-sensitive dye and imaged stimulus-evoked calcium influx in a slice preparation. Single olfactory nerve shocks evoked rapid fluorescence increases that were largely blocked by the N-type calcium channel blocker omega-conotoxin GVIA. Paired shocks revealed a long-lasting suppression of calcium influx with approximately 40% suppression at 400-ms interstimulus intervals and a recovery time constant of approximately 450 ms. Blocking activation of postsynaptic olfactory bulb neurons with APV/CNQX reduced this suppression. The GABA(B) receptor agonist baclofen inhibited calcium influx, whereas GABA(B) antagonists reduced paired-pulse suppression without affecting the response to the conditioning pulse. We also imaged transmitter release directly using a mouse line that expresses synaptopHluorin selectively in ORNs. We found that the relationship between calcium influx and transmitter release was superlinear and that paired-pulse suppression of transmitter release was reduced, but not eliminated, by APV/CNQX and GABA(B) antagonists. These results demonstrate that primary olfactory input to the CNS can be presynaptically regulated by GABAergic interneurons and show that one major intracellular pathway for this regulation is via the suppression of calcium influx through N-type calcium channels in the presynaptic terminal. This mechanism is unique among primary sensory afferents.
authors.affiliation: Department of Biology, Boston University, MA 02215, USA. dmattw@bu.edu
authors.forename: Matt
authors.initials: M
authors.lastname: Wachowiak
authors.forename: John P
authors.initials: JP
authors.lastname: McGann
authors.forename: Philip M
authors.initials: PM
authors.lastname: Heyward
authors.forename: Zuoyi
authors.initials: Z
authors.lastname: Shao
authors.forename: Adam C
authors.initials: AC
authors.lastname: Puche
authors.forename: Michael T
authors.initials: MT
authors.lastname: Shipley
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D005456:Fluorescent Dyes / Q000378:metabolism; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009830:Olfactory Bulb / Q000166:cytology*; D009833:Olfactory Pathways / Q000502:physiology*; D018034:Olfactory Receptor Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques / Q000379:methods; D010721:Phosphinic Acids / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism*; D011412:Propanolamines / Q000494:pharmacology; D013997:Time Factors; D020866:omega-Conotoxin GVIA / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D018691:Excitatory Amino Acid Antagonists; D005456:Fluorescent Dyes; D018755:GABA Agonists; D018756:GABA Antagonists; D009419:Nerve Tissue Proteins; D010721:Phosphinic Acids; D011412:Propanolamines; C485506:synapto-pHluorin protein, mouse; C085075:CGP 55845A; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; D020866:omega-Conotoxin GVIA; D001418:Baclofen; D002118:Calcium