title: Discharge of the hypoglossal nerve cannot distinguish eupnea from gasping, as defined by phrenic discharge, in the in situ mouse.
abstract: If normal, eupneic breathing fails, gasping is recruited. Serotonin was proposed as essential for gasping, based on findings using an in vitro mouse preparation. This preparation generates rhythmic activities of the hypoglossal nerve that are considered to be akin to both eupnea and gasping. In previous studies, gasping of in situ rat and mouse preparations continued unabated following blockers of receptors for serotonin. However, hypoglossal activity was not recorded in the mouse, and we hypothesized that its discharge during gasping might be dependent on serotonin. In the in situ mouse preparation, hypoglossal discharge had varying and inconsistent patterns during eupnea, discharging concomitant with the phrenic burst, at varying intervals between phrenic bursts, or was silent in some respiratory cycles. In eupnea, phrenic discharge was incrementing, whereas hypoglossal discharge was decrementing in 15 of 20 preparations. During ischemia-induced gasping, peak phrenic height was reached at 205 +/- 17 ms, compared with 282 +/- 27.9 ms after the start of the eupneic burst (P < 0.002). In contrast, rates of rise of hypoglossal discharge in gasping (peak at 233 +/- 25 ms) and eupnea (peak at 199 +/- 19.2 ms) were the same. The uncoupling of hypoglossal from phrenic discharge in eupnea was exacerbated by methysergide, an antagonist of serotonin receptors. These findings demonstrate that hypoglossal discharge alone cannot distinguish eupnea from gasping nor, in eupnea, can hypoglossal activity be used to differentiate neural inspiration from expiration. These findings have significant negative implications for conclusions drawn from the in vitro medullary slice of mouse.
authors.affiliation: Department of Physiology, Dartmouth Medical School, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire 03756, USA. walter.m.stjohn@dartmouth.edu
authors.forename: Walter M
authors.initials: WM
authors.lastname: St John
authors.forename: J C
authors.initials: JC
authors.lastname: Leiter
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D003391:Cranial Nerves / Q000502:physiology; D004576:Electromyography; D007002:Hypoglossal Nerve / Q000502:physiology*; D000860:Hypoxia / Q000503:physiopathology; D007511:Ischemia / Q000503:physiopathology; D008784:Methysergide / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D010791:Phrenic Nerve / Q000502:physiology*; D015656:Respiratory Mechanics / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013127:Spinal Nerves / Q000502:physiology; D014630:Vagus Nerve / Q000502:physiology
chemical_list: D012702:Serotonin Antagonists; D000251:Adenosine Triphosphatases; D000074183:ATPases Associated with Diverse Cellular Activities; C495989:Pex1 protein, mouse; D008784:Methysergide