Faculty Opinions recommendation of Spatial and functional architecture of the mammalian brain stem respiratory network: a hierarchy of three oscillatory mechanisms.

Author(s):  
James Duffin
2007 ◽  
Vol 98 (6) ◽  
pp. 3370-3387 ◽  
Author(s):  
J. C. Smith ◽  
A. P. L. Abdala ◽  
H. Koizumi ◽  
I. A. Rybak ◽  
J. F. R. Paton

Mammalian central pattern generators (CPGs) producing rhythmic movements exhibit extremely robust and flexible behavior. Network architectures that enable these features are not well understood. Here we studied organization of the brain stem respiratory CPG. By sequential rostral to caudal transections through the pontine-medullary respiratory network within an in situ perfused rat brain stem–spinal cord preparation, we showed that network dynamics reorganized and new rhythmogenic mechanisms emerged. The normal three-phase respiratory rhythm transformed to a two-phase and then to a one-phase rhythm as the network was reduced. Expression of the three-phase rhythm required the presence of the pons, generation of the two-phase rhythm depended on the integrity of Bötzinger and pre-Bötzinger complexes and interactions between them, and the one-phase rhythm was generated within the pre-Bötzinger complex. Transformation from the three-phase to a two-phase pattern also occurred in intact preparations when chloride-mediated synaptic inhibition was reduced. In contrast to the three-phase and two-phase rhythms, the one-phase rhythm was abolished by blockade of persistent sodium current ( INaP). A model of the respiratory network was developed to reproduce and explain these observations. The model incorporated interacting populations of respiratory neurons within spatially organized brain stem compartments. Our simulations reproduced the respiratory patterns recorded from intact and sequentially reduced preparations. Our results suggest that the three-phase and two-phase rhythms involve inhibitory network interactions, whereas the one-phase rhythm depends on INaP. We conclude that the respiratory network has rhythmogenic capabilities at multiple levels of network organization, allowing expression of motor patterns specific for various physiological and pathophysiological respiratory behaviors.


2016 ◽  
Vol 115 (5) ◽  
pp. 2593-2607 ◽  
Author(s):  
Sarah E. Jones ◽  
Mathias Dutschmann

Degeneracy of respiratory network function would imply that anatomically discrete aspects of the brain stem are capable of producing respiratory rhythm. To test this theory we a priori transected brain stem preparations before reperfusion and reoxygenation at 4 rostrocaudal levels: 1.5 mm caudal to obex ( n = 5), at obex ( n = 5), and 1.5 ( n = 7) and 3 mm ( n = 6) rostral to obex. The respiratory activity of these preparations was assessed via recordings of phrenic and vagal nerves and lumbar spinal expiratory motor output. Preparations with a priori transection at level of the caudal brain stem did not produce stable rhythmic respiratory bursting, even when the arterial chemoreceptors were stimulated with sodium cyanide (NaCN). Reperfusion of brain stems that preserved the pre-Bötzinger complex (pre-BötC) showed spontaneous and sustained rhythmic respiratory bursting at low phrenic nerve activity (PNA) amplitude that occurred simultaneously in all respiratory motor outputs. We refer to this rhythm as the pre-BötC burstlet-type rhythm. Conserving circuitry up to the pontomedullary junction consistently produced robust high-amplitude PNA at lower burst rates, whereas sequential motor patterning across the respiratory motor outputs remained absent. Some of the rostrally transected preparations expressed both burstlet-type and regular PNA amplitude rhythms. Further analysis showed that the burstlet-type rhythm and high-amplitude PNA had 1:2 quantal relation, with burstlets appearing to trigger high-amplitude bursts. We conclude that no degenerate rhythmogenic circuits are located in the caudal medulla oblongata and confirm the pre-BötC as the primary rhythmogenic kernel. The absence of sequential motor patterning in a priori transected preparations suggests that pontine circuits govern respiratory pattern formation.


2002 ◽  
Vol 283 (4) ◽  
pp. L665-L670 ◽  
Author(s):  
Jay B. Dean ◽  
David Ballantyne ◽  
Daniel L. Cardone ◽  
Joseph S. Erlichman ◽  
Irene C. Solomon

Gap junctions are composed of connexins, which are organized into intercellular channels that form transmembrane pathways between neurons (cell-cell coupling), and in some cases, neurons and glia, for exchange of ions and small molecules (metabolic coupling) and ionic current (electrical coupling). Cell-cell coupling via gap junctions has been identified in brain stem neurons that function in CO2/H+ chemoreception and respiratory rhythmogenesis; however, the exact roles of gap junctions in respiratory control are undetermined. Here we review the methods commonly used to study gap junctions in the mammalian brain stem under in vitro and in vivo conditions and briefly summarize the anatomical, pharmacological, and electrophysiological evidence to date supporting roles for cell-cell coupling in respiratory rhythmogenesis and central chemoreception. Specific research questions related to the role of gap junctions in respiratory control are suggested for future research.


2012 ◽  
Vol 22 (05) ◽  
pp. 1250114 ◽  
Author(s):  
LIXIA DUAN ◽  
DEHONG ZHAI ◽  
XUHUI TANG

In this paper, we study and classify the bursting in a two-cell network of excitatory neuron within the pre-Bötzinger complex of the mammalian brain stem. We investigate the effects of parameters g Na and g K on the bursting generation and pattern transitions in the two-cell model network with synaptic coupling by the fast–slow decomposition and bifurcation analysis approach. Comparing the firing patterns of the uncoupled and coupled cells, we found that the bursting patterns are the same both for a single and two-cell model network with the parameter g Na changed, while they are different with the parameter g K changed. Our results are instructive for further understanding the dependence of the complex firing activities of the network on the firing activities of the single cell in the network.


1988 ◽  
Vol 2 (7) ◽  
pp. 2283-2288 ◽  
Author(s):  
Jeffrey C. Smith ◽  
Jack L. Feldman ◽  
Brian J. Schmidt

2008 ◽  
Vol 104 (6) ◽  
pp. 1801-1808 ◽  
Author(s):  
Qiuli Liu ◽  
Margaret T. T. Wong-Riley

Previously, we reported a critical period [around postnatal day (P) 12– 13 in the rat] in respiratory network development when distinct neurochemical, metabolic, and physiological changes occur. Since serotonin 2A (5-HT2A) receptors play an important role in respiratory modulation, we hypothesized that they may undergo developmental adjustments during the critical period. Semi-quantitative immunohistochemical analyses were conducted in labeled neurons in a number of brain stem nuclei with or without known respiratory functions from P2 to P21 in rats. Our data indicate that the expressions of 5-HT2A receptors in neurons of the pre-Bötzinger complex, the nucleus ambiguus, and the hypoglossal nucleus were maintained within a relatively narrow range between P2 and P21, with a dip at P3–P4 and a significant reduction only at P12. This change was not observed in the nonrespiratory cuneate nucleus. These results suggest that reduced expressions of 5-HT2A receptors at P12 contributes to neurochemical imbalance within brain stem respiratory nuclei at that time and may be involved in decreased hypoxic ventilatory response at this critical period of development.


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