UBC Theses and Dissertations
The role of the parabrachial/Kolliker Fuse respiratory complex in the control of respiration Boon, Joyce A.
My goal was to explore the role of the parabrachial/Kölliker Fuse region (PBrKF) of the pons in the production of "state-related" changes in breathing in rats. I hypothesized that the effects of changes in cortical activation state on breathing and respiratory sensitivity are relayed from the pontine reticular formation to the respiratory centres of the medulla via the PBrKF. I found that urethane anaesthetized Sprague Dawley rats spontaneously cycled between a cortically desynchronized state (State I) and a cortically synchronized state (State III), which were very similar to awake and slow wave sleep (SWS) states in unanaesthetized animals, based on EEG criteria. Urethane produced no significant respiratory depression or reduction in sensitivity to hypoxia or hypercapnia. However, breathing frequency (f[sub R]), tidal volume (V[sub T] ) and total ventilation (V[sub TOT]) all increased on cortical activation, and changes in the relative sensitivity to hypoxia and hypercapnia with changes in state were similar to those seen in unanaesthetized rats. This indicated that the urethane model of sleep and wakefulness could be used to investigate the effects of cortical activation state on respiration. Since NMDA-type glutamate receptor mediated processes in the PBrKF are known to be important in respiratory control, I examined the role of the PBrKF as a relay site for state effects on respiration by blocking neurons with NMDA-type glutamate receptors with MK-801. I first used systemic blockade and found that it altered resting ventilation and modified the hypoxic, but not the hypercapnic ventilatory response, as has been reported in unanaesthetized animals. Microinjection of MK-801 into the PBrKF confirmed that the 'wakefulness' stimulus for breathing involved glutamate activation of NMDAr on PBrKF neurons, but these neurons were not involved in the response to either continuous or intermittent hypoxia, nor did they change chemosensitivity on cortical activation. However, they indirectly modulated the HVR by altering cortical activation state as animals cycled between State I during hypoxia, and State III post hypoxia. NMDAr in the PBrKF also functioned to return tidal volume to normal following hypoxia and in so doing, prevented the development of long-term facilitation of breathing.
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