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The Journal of Neuroscience, August 1, 2000, 20(15):5858-5866
Role of Inspiratory Pacemaker Neurons in Mediating the Hypoxic
Response of the Respiratory Network In Vitro
Muriel
Thoby-Brisson and
Jan-Marino
Ramirez
Department of Organismal Biology and Anatomy, Committee on
Neurobiology, The University of Chicago, Chicago, Illinois 60637
In severe hypoxia the breathing frequency is modulated in a
biphasic manner: an initial increase (augmentation) is followed by a
depression and cessation of breathing (apnea). Using a mouse slice
preparation that contains the functional respiratory network, we aimed
at identifying the neurons responsible for this frequency modulation.
Whole-cell patch recordings revealed that expiratory neurons become
tonically active during anoxia, indicating that these neurons cannot be
responsible for the respiratory frequency modulation. Inspiratory
neurons tended to depolarize (by 6.9 mV; n = 9),
and the frequency of rhythmic activity was significantly increased
during anoxia (from 0.16 to 0.4 Hz; n = 9). After
the blockade of network activity with
6-cyano-7-nitroquinoxaline-2,3-dione, most inspiratory neurons became
tonically active (72%; n = 25, non-pacemaker). In
anoxia, the membrane potential of these non-pacemaker neurons did not
change ( 0.26 mV; n = 6), and their tonic activity ceased. Only a subpopulation of inspiratory neurons remained
rhythmically active in the absence of network activity (pacemaker
neurons, 28%, 7 of 25 inspiratory neurons). In anoxia two subgroups of pacemaker neurons were differentiated; one group showed a transient increase in the bursting activity, followed by a decrease and cessation
of rhythmic activity. These neurons tended to depolarize (by 10.3 mV)
during anoxia. The second group remained rhythmic during the entire
anoxic exposure and exhibited no depolarization. The time course of the
frequency modulation in all pacemaker neurons resembled that of the
intact network. We conclude that pacemaker neurons are primarily
responsible for the frequency modulation in anoxia and that in the
respiratory network there is a strict separation between rhythm- and
pattern-generating mechanisms.
Key words:
pacemaker neurons; hypoxic response; respiratory; apnea; augmentation; anoxia
Copyright © 2000 Society for Neuroscience 0270-6474/00/20155858-09$05.00/0
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