Synaptically activated burst-generating conductances may underlie a group-pacemaker mechanism for respiratory rhythm generation in mammals.
Breathing, chewing, and walking are critical life-sustaining behaviors in mammals that consist essentially of simple rhythmic movements. Breathing movements in particular involve the diaphragm, thorax, and airways but emanate from a network in the lower brain stem. This network can be studied in reduced preparations in vitro and using simplified mathematical models that make testable predictions. An iterative approach that employs both in vitro and in silico models argues against canonical mechanisms for respiratory rhythm in neonatal rodents that involve reciprocal inhibition and pacemaker properties. We present an alternative model in which emergent network properties play a rhythmogenic role. Specifically, we show evidence that synaptically activated burst-generating conductances-which are only available in the context of network activity-engender robust periodic bursts in respiratory neurons. Because the cellular burst-generating mechanism is linked to network synaptic drive we dub this type of system a group pacemaker.
Department of Applied Science, McGlothlin-Street Hall, The College of William & Mary, Williamsburg, Virginia, USA.
Christopher A
CA
Del Negro
John A
JA
Hayes
Ryland W
RW
Pace
Benjamin R
BR
Brush
Ryoichi
R
Teruyama
Jack L
JL
Feldman
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001683:Biological Clocks / Q000502:physiology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D058785:GABA-A Receptor Agonists / Q000494:pharmacology; D015640:Ion Channel Gating; D007473:Ion Channels / Q000378:metabolism; D008526:Medulla Oblongata / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology; D009118:Muscimol / Q000494:pharmacology; D009415:Nerve Net / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D010507:Periodicity; D012119:Respiration / Q000187:drug effects; D019782:Riluzole / Q000494:pharmacology; D013569:Synapses / Q000502:physiology*; D050053:TRPM Cation Channels / Q000235:genetics / Q000378:metabolism
D018691:Excitatory Amino Acid Antagonists; D058785:GABA-A Receptor Agonists; D007473:Ion Channels; D050053:TRPM Cation Channels; D009118:Muscimol; D019782:Riluzole