Serotonergic modulation of inspiratory hypoglossal motoneurons in decerebrate dogs.
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.
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, USA.
Ivo F
IF
Brandes
Edward J
EJ
Zuperku
Astrid G
AG
Stucke
Danica
D
Jakovcevic
Francis A
FA
Hopp
Eckehard A E
EA
Stuth
D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D001683:Biological Clocks / Q000502:physiology; D003655:Decerebrate State / Q000503:physiopathology*; D004285:Dogs; D005246:Feedback / Q000502:physiology; D007002:Hypoglossal Nerve / Q000502:physiology*; D001239:Inhalation / Q000502:physiology*; D009046:Motor Neurons / Q000502:physiology*; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*
D044402:Receptor, Serotonin, 5-HT2A; D012701:Serotonin