The Parabrachial Nucleus and Kölliker‐Fuse Nucleus contribute jointly to inspiratory and expiratory phase duration

Abstract

The Parabrachial Nucleus (PBN)/ Kölliker‐Fuse (KF) complex are important subareas of the ventral respiratory column (VRC) that regulate inspiratory (1) and expiratory (2) phase off‐switch. Our goal was to determine whether the effects on phase duration of these two adjacent areas were specific for each area and independent of each other. The study was approved by the local Animal Care Committee and conformed to NIH standards. Adult New Zealand White rabbits (3–4 kg) were anesthetized, tracheotomized, ventilated, decerebrated and vagotomized. Phrenic nerve activity was recorded from the c5 rootlet, time averaged and used to calculate inspiratory and expiratory durations. Gridwise localized pressure microinjections of α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA, 50 μM, 70 nl) utilizing a multibarrel glass pipette with a tip diameter of 20μm into the VRC caudal to the inferior collicle identified two areas with distinctly different pattern changes: An area (on average 1mm caudal from inferior collicle, 2mm lateral from midline, 7 mm ventral to the dorsal surface) where AMPA injection caused significant tachypnea with increased peak phrenic activity (PPA) was identified as the PBN, and a second area (on average 1mm caudal, 0.5–1mm lateral and 2mm ventral to the PBN) where AMPA caused transient bradypnea and a decrease in PPA was identified as the KF. In ten animals, injection of the glutamate receptor antagonists (2,3‐dihydroxy‐6‐nitro‐7‐sulfamoyl‐benzo[f]quinoxaline) (NBQX, 1mM, 700nl) and (2R)‐amino‐5‐phosphonovaleric acid (AP5, 5mM, 700nl) into the KF area increased inspiratory (TI) and expiratory (TE) duration significantly from 0.8±0.1 to 8.7±3 sec (p=0.006, 2‐way ANOVA, factors: location, drug; mean±SE) and 1.2±0.1 to 8.5±2.7 sec (p=0.011), resp. Respiratory rate (RR) decreased from 32±3 bpm to 9±2 bpm (p<0.001) and peak phrenic activity (PPA) decreased from 100% to 89±3% (p=0.028). Subsequent glutamatergic block in the PBN caused an additional increase in TI to 18.8±3.4 sec (p<0.001) and TE to 23.5±3 sec (p<0.001). Respiratory rate was decreased to 2±1 bpm (p=0.009) without further change in PPA (83±6%, p=0.463). In six animals block of glutamatergic excitation first in the PBN and then in the KF resulted in similar overall effects (TI 0.8±0.1 to 20.9±6.1sec, TE 1.1±0.2 to 18.3±5.5sec, RR 36±6 to 5±3bpm, PPA 100 to 85±7%). While in some animals KF injections had greater effects on TI and PBN injections greater effects on TE, these differences were minor. Generally, the increases in TI and TE tracked closely suggesting that both, the KF and PBN contribute significantly to the inspiratory and expiratory off‐switch mechanism.Support or Funding InformationR01GM112960‐01A1 (Dr. Stucke) and VA merit grant I01BX000721 (Dr. Zuperku)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.