title: Mixed-mode oscillations and population bursting in the pre-Bötzinger complex.
abstract: This study focuses on computational and theoretical investigations of neuronal activity arising in the pre-Bötzinger complex (pre-BötC), a medullary region generating the inspiratory phase of breathing in mammals. A progressive increase of neuronal excitability in medullary slices containing the pre-BötC produces mixed-mode oscillations (MMOs) characterized by large amplitude population bursts alternating with a series of small amplitude bursts. Using two different computational models, we demonstrate that MMOs emerge within a heterogeneous excitatory neural network because of progressive neuronal recruitment and synchronization. The MMO pattern depends on the distributed neuronal excitability, the density and weights of network interconnections, and the cellular properties underlying endogenous bursting. Critically, the latter should provide a reduction of spiking frequency within neuronal bursts with increasing burst frequency and a dependence of the after-burst recovery period on burst amplitude. Our study highlights a novel mechanism by which heterogeneity naturally leads to complex dynamics in rhythmic neuronal populations.
authors.affiliation: Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, United States.
authors.forename: Bartholomew J
authors.identifier: http://orcid.org/0000-0003-0727-3928
authors.initials: BJ
authors.lastname: Bacak
authors.affiliation: Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, United States.
authors.forename: Taegyo
authors.initials: T
authors.lastname: Kim
authors.affiliation: Cellular and Systems Neurobiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, United States.
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Smith
authors.affiliation: Department of Mathematics, University of Pittsburgh, Pittsburgh, United States.
authors.forename: Jonathan E
authors.identifier: http://orcid.org/0000-0002-1513-1551
authors.initials: JE
authors.lastname: Rubin
authors.affiliation: Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, United States.
authors.forename: Ilya A
authors.identifier: http://orcid.org/0000-0003-3461-349X
authors.initials: IA
authors.lastname: Rybak
mesh_terms: D000200:Action Potentials; D000818:Animals; D001683:Biological Clocks; D001239:Inhalation; D007395:Interneurons / Q000502:physiology*; D008322:Mammals; D008959:Models, Neurological; D008962:Models, Theoretical; D009415:Nerve Net; D012125:Respiratory Center / Q000166:cytology*; D020651:Ventral Thalamic Nuclei / Q000166:cytology*
keywords: central pattern generator; computational biology; computational modeling; mixed-mode oscillations; neural oscillations; neuroscience; none; pre-Bӧtzinger complex; respiration; systems biology