- ORAL PRESENTATIONS - SESSION 2
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Central mechanisms controlling upper airway patency
Respiratory Researchvolume 2, Article number: 2.4 (2001)
The neurones of the ponto-medullary respiratory network drive two functionally and anatomically distinct pools of motoneurones. One set is located within the spinal cord that innervates the diaphragm and intercostal muscles. A second group of motoneurones is located within the nucleus ambiguus imbedded in the ventral respiratory group that project via cranial motor outflows to co-ordinate the activity of laryngeal and bronchial muscles to control airway resistance and airflow. These spinal and cranial motor activities have to be precisely co-ordinated to ensure efficient ventilation. We recently included this behaviour as imperative for a definition of eupnoea. Thus, beside a rhythmic eupnoeic (ramp) discharge pattern of pump motoneurones, a phasic respiratory modulation of glottal resistance should be observed and expressed as glottal dilation during inspiration and transient glottal constriction during post-inspiration . During the last decade mechanisms underlying respiratory rhythm generation were studied primarily in reduced in vitro preparations. The work concluded that the respiratory rhythm is generated by pacemaker neurones located in the Pre-Bötzinger complex and is independent of inhibitory glycinergic synaptic transmission (for review see [2,3]). However, a potential role for glycinergic transmission for the eupneic co-ordination of circuitry controlling the upper airway was largely disregarded.
To determine a role for glycinergic inhibition within the pon-tomedullary network, we used the arterially perfused working heart-brainstem preparation (WHBP) of neonatal and mature rat. This preparation allows both kinesiological and cellular studies of central and peripheral mechanisms controlling upper airway resistance . Recording of the recurrent laryngeal nerve activity as an index of motor output to the glottis revealed post-inspiratory activity that shifted towards the inspiratory phase after strychnine antagonism of glycine receptors (0.5–1.5 μM). This shift of post-inspiratory activity was also obtained at the cellular level: intracellular recordings of post-inspiratory neurones revealed that the hyperpo-larisation during the inspiratory phase was converted to a depolarisation with spike discharge after exposure to strychnine. This lead to a massive disturbance of the eupnoeic modulation of glottal resistance by converting the inspiratory glottic dilatation (seen during control) to a paradoxical constriction, as demonstrated by measuring changes in laryngeal resistance. Similar results were obtained in both neonatal and juvenile rats suggesting that glycinergic mechanisms co-ordinating ventilatory movements with upper airway resistance are functional at birth. The effects of glycinergic inhibition were mimicked during exposure of neonatal preparations to prolonged hypoxia. During the secondary hypoxic depression of respiration post-inspiratory activity was shifted towards inspiration causing a paradoxical glottic constriction during neural inspiration. We conclude that integrity of glycinergic neurotransmission within the ponto-medullary respiratory network is essential for co-ordinating the neuronal activities which control upper airway resistance and ventilatory movements and consequently the eupnoeic breathing pattern in rats from birth.
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Smith JC, Butera RJ, Koshiya N, Del Negro C, Wilson CG, Johnson SM: Respiratory rhythm generation in neonatal and adult mammals: the hybrid pacemaker-network model. Respir Physiol. 2000, 122: 131-47. 10.1016/S0034-5687(00)00155-9.
This work was founded by the Deutsche Forschungsgemeinschaft and the British Heart Foundation and was approved by the University Animal Ethics Committee.