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The Journal of Neuroscience, April 15, 2003, 23(8):3538
Stabilization of Bursting in Respiratory Pacemaker Neurons
Andrew K.
Tryba,
Fernando
Peña, and
Jan-Marino
Ramirez
The University of Chicago, Department of Organismal Biology and
Anatomy, Chicago, Illinois 60637
Synaptic and endogenous pacemaker properties have been
hypothesized as principal cellular mechanisms for respiratory rhythm generation. This rhythmic activity is thought to originate in the
pre-Bötzinger complex, an area that can generate fictive respiration when isolated in brainstem slice preparations of mice. In
slice preparations, external potassium concentration
([K+]o) is typically elevated
from 3 to 8 mM to induce rhythmic population activity.
However, elevated [K+]o may not simply
depolarize respiratory neurons but also change rhythm-generating
mechanisms by inducing or altering pacemaker properties. To test this,
we examined the membrane potential
(Vm) of nonpacemaker neurons and
endogenous bursting properties of pacemaker neurons before and after
blockade of excitatory and inhibitory synaptic input in 3 mM [K+]o artificial CSF
(aCSF). Most pacemaker neurons (82%) ceased to burst in 3 mM [K+]o aCSF after
blockade of glutamatergic transmission. In all of these, endogenous
bursting was restored on additional blockade of glycinergic and
GABAergic inhibition. Thus, bursting properties are suppressed by
endogenous synaptic inhibition, the level of which may determine
whether network rhythmicity is generated in 3 mM
(n = 12) or 8 mM (n = 40) [K+]o aCSF. In 3 mM
[K+]o aCSF, synaptically isolated
pacemaker neurons (n = 22) continued to burst over
a wide range of imposed Vm. Furthermore, the
Vm of synaptically isolated pacemaker
neurons was not significantly affected (p = 0.1; n = 10) when
[K+]o was changed from 8 to 3 mM, whereas isolated nonpacemakers hyperpolarized
(p < 0.001; n = 14). We
conclude that respiratory pacemaker neurons possess membrane properties
that stabilize their bursting against changes in
[K+]o and imposed changes in
Vm.
Key words:
respiration; pacemaker properties; pattern
generation; pre-Bötzinger complex; rhythm generation; potassium
concentration
Copyright © 2003 Society for Neuroscience 0270-6474/03/2383538-09$05.00/0
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