title: Peripheral oxygen-sensing cells directly modulate the output of an identified respiratory central pattern generating neuron.
abstract: Breathing is an essential homeostatic behavior regulated by central neuronal networks, often called central pattern generators (CPGs). Despite ongoing advances in our understanding of the neural control of breathing, the basic mechanisms by which peripheral input modulates the activities of the central respiratory CPG remain elusive. This lack of fundamental knowledge vis-à-vis the role of peripheral influences in the control of the respiratory CPG is due in large part to the complexity of mammalian respiratory control centres. We have therefore developed a simpler invertebrate model to study the basic cellular and synaptic mechanisms by which a peripheral chemosensory input affects the central respiratory CPG. Here we report on the identification and characterization of peripheral chemoreceptor cells (PCRCs) that relay hypoxia-sensitive chemosensory information to the known respiratory CPG neuron right pedal dorsal 1 in the mollusk Lymnaea stagnalis. Selective perfusion of these PCRCs with hypoxic saline triggered bursting activity in these neurons and when isolated in cell culture these cells also demonstrated hypoxic sensitivity that resulted in membrane depolarization and spiking activity. When cocultured with right pedal dorsal 1, the PCRCs developed synapses that exhibited a form of short-term synaptic plasticity in response to hypoxia. Finally, osphradial denervation in intact animals significantly perturbed respiratory activity compared with their sham counterparts. This study provides evidence for direct synaptic connectivity between a peripheral regulatory element and a central respiratory CPG neuron, revealing a potential locus for hypoxia-induced synaptic plasticity underlying breathing behavior.
authors.affiliation: Department of Cell Biology and Anatomy, Faculty of Medicine, University of Calgary, NW, Calgary, Alberta, Canada, T2N 4N1. harold.bell@ucalgary.ca
authors.forename: Harold J
authors.initials: HJ
authors.lastname: Bell
authors.forename: Takuya
authors.initials: T
authors.lastname: Inoue
authors.forename: Kelly
authors.initials: K
authors.lastname: Shum
authors.forename: Collin
authors.initials: C
authors.lastname: Luk
authors.forename: Naweed I
authors.initials: NI
authors.lastname: Syed
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000969:Antinematodal Agents / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000166:cytology*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation / Q000379:methods; D017952:Ganglia, Invertebrate / Q000166:cytology*; D000860:Hypoxia / Q000503:physiopathology; D066298:In Vitro Techniques; D008274:Magnesium / Q000494:pharmacology; D008464:Mecamylamine / Q000494:pharmacology; D009415:Nerve Net / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D009474:Neurons / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D010100:Oxygen / Q000378:metabolism* / Q000494:pharmacology; D012119:Respiration / Q000187:drug effects; D012908:Snails; D013498:Suramin / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
chemical_list: D000969:Antinematodal Agents; D018733:Nicotinic Antagonists; D013498:Suramin; D008464:Mecamylamine; D008274:Magnesium; D010100:Oxygen