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Triple Oscillator Hypothesis: Three Excitatory Rhythm Generating Networks Control the Three Phases of Breathing
Author(s) -
Anderson Tatiana M.,
Garcia Alfredo J.,
Baertsch Nathan A.,
Pollak Julia,
Ramirez JanMarino
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.729.7
Subject(s) - excitatory postsynaptic potential , neuroscience , nucleus ambiguus , inhibitory postsynaptic potential , population , slice preparation , biology , chemistry , medulla oblongata , medicine , electrophysiology , central nervous system , environmental health
Breathing is composed of three phases: inspiration, postinspiration, and active expiration. Excitatory rhythm generating networks have been identified for the generation of inspiration, the preBötzinger complex (preBötC), and for active expiration, the lateral parafacial (pF L ). By utilizing a combination of a new in vitro horizontal slice preparation, optogenetics, and in vivo techniques, we have recently identified and characterized a novel population of neurons that we show to be necessary and sufficient for the generation of postinspiration (Anderson et al. 2016). This network, located dorsomedial to the nucleus ambiguus and caudal to the facial nucleus, is referred to as the postinspiratory complex, or PiCo. PiCo can function as an independent oscillator dependent on excitatory, non‐NMDA mechanisms. Here we show that a subpopulation of PiCo neurons are endowed with I CAN and I NaP dependent pacemaker properties, suggesting that PiCo has similar rhythm generating properties to the preBötC. Additionally, we observed differential effects of inhibitory antagonists. When strychnine, a glycine receptor antagonist, was bath applied to the horizontal slice in vitro, the burst duration of fictive inspiratory preBötC bursts significantly decreased while PiCo burst duration was unchanged. Upon the additional application of gabazine, a GABAergic receptor antagonist, the two rhythms progressively synchronized. Furthermore, in the presence of gabazine, the average burst area and amplitude significantly increased for both preBötC and PiCo rhythms. Based on our discovery, we propose a triple‐oscillator hypothesis that states that the three phases of respiration are generated by three, anatomically distinct, excitatory, rhythmogenic and interactive networks: the preBötC, PiCo, and PF L . We further conclude that network inhibition serves to coordinate the timing, phasing and patterning of these rhythms. Support or Funding Information 1F31NS087828‐01 RO1 HL107084‐01