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Serotonergic modulation of inspiratory hypoglossal motoneurons in decerebrate dogs. J Neurophysiol 2006 Jun;95(6):3449-59

Date

02/24/2006

Pubmed ID

16495364

Pubmed Central ID

PMC2582383

DOI

10.1152/jn.00823.2005

Scopus ID

2-s2.0-33744938895 (requires institutional sign-in at Scopus site)   29 Citations

Abstract

Inspiratory hypoglossal motoneurons (IHMNs) maintain upper airway patency. However, this may be compromised during sleep and by sedatives, potent analgesics, and volatile anesthetics by either depression of excitatory or enhancement of inhibitory inputs. In vitro data suggest that serotonin (5-HT), through the 5-HT2A receptor subtype, plays a key role in controlling the excitability of IHMNs. We hypothesized that in vivo 5-HT modulates IHMNs activity through the 5-HT2A receptor subtype. To test this hypothesis, we used multibarrel micropipettes for extracellular single neuron recording and pressure picoejection of 5-HT or ketanserin, a selective 5-HT2A receptor subtype antagonist, onto single IHMNs in decerebrate, vagotomized, paralyzed, and mechanically ventilated dogs. Drug-induced changes in neuronal discharge frequency (F(n)) and neuronal discharge pattern were analyzed using cycle-triggered histograms. 5-HT increased the control peak F(n) to 256% and the time-averaged F(n) to 340%. 5-HT increased the gain of the discharge pattern by 61% and the offset by 34 Hz. Ketanserin reduced the control peak F(n) by 68%, the time-averaged F(n) by 80%, and the gain by 63%. These results confirm our hypothesis that in vivo 5-HT is a potent modulator of IHMN activity through the 5-HT2A receptor subtype. Application of exogenous 5-HT shows that this mechanism is not saturated during hypercapnic hyperoxia. The two different mechanisms, gain modulation and offset change, indicate that 5-HT affects the excitability as well as the excitation of IHMNs in vivo.

Author List

Brandes IF, Zuperku EJ, Stucke AG, Jakovcevic D, Hopp FA, Stuth EA

Authors

Astrid G. Stucke MD Professor in the Anesthesiology department at Medical College of Wisconsin
Eckehard A. Stuth MD Professor in the Anesthesiology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Action Potentials
Animals
Biological Clocks
Decerebrate State
Dogs
Feedback
Hypoglossal Nerve
Inhalation
Motor Neurons
Receptor, Serotonin, 5-HT2A
Serotonin