State-Dependent Interactions between Excitatory Neuromodulators in the Neuronal Control of Breathing
Open Access
- 16 June 2010
- journal article
- Published by Society for Neuroscience in Journal of Neuroscience
- Vol. 30 (24), 8251-8262
- https://doi.org/10.1523/JNEUROSCI.5361-09.2010
Abstract
All neuronal networks are modulated by multiple neuropeptides and biogenic amines. Yet, few studies investigate how different modulators interact to regulate network activity. Here we explored the state-dependent functional interactions between three excitatory neuromodulators acting on neurokinin1 (NK1), α1 noradrenergic (α1 NE), and 5-HT2 serotonin receptors within the pre-Bötzinger complex (pre-BötC), an area critical for the generation of breathing. In anesthetized, in vivo mice, the reliance on endogenous NK1 activation depended on spontaneous breathing frequency and the modulatory state of the animal. Endogenous NK1 activation had no significant respiratory effect when stimulating raphe magnus and/or locus ceruleus, but became critical when α1 NE and 5-HT2 receptors were pharmacologically blocked. The dependence of the centrally generated respiratory rhythm on NK1 activation was blunted in the presence of α1 NE and 5-HT2 agonists as demonstrated in slices containing the pre-BötC. We conclude that a modulator9s action is determined by the concurrent modulation and interaction with other neuromodulators. Deficiencies in one neuromodulator are immediately compensated by the action of other neuromodulators. This interplay could play a role in the state dependency of certain breathing disorders.This publication has 93 references indexed in Scilit:
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