Synaptic events in ventral respiratory neurones during apnoea induced by laryngeal nerve stimulation in neonatal pig.

Abstract

SUMMARY1. Postsynaptic potentials evoked by electrical stimulation of superior laryngeal nerve (SLN) were recorded during SLN-induced apnoea from the respiratory neurones of the ventral respiratory group (VRG) in pentobarbitone-anaesthetized, vagotomized and artificially ventilated newborn piglets (n = 14, 4-7 days old). All recorded inspiratory (n = 10), post-inspiratory (n = 10) and expiratory (n = 20) neurones had a triphasic pattern of membrane potential and were identified for their projections to the spinal cord or cervical vagus nerve.2. During long-lasting apnoea, induced by SLN stimulation, the membrane potential trajectory of each type of recorded neurone was held at the level corresponding approximately to the membrane potential reached during stage I of expiration. Compound postsynaptic potentials evoked in most respiratory-related neurones had an early short-lasting and a late long-lasting component.3. Postsynaptic potentials in four out of seven inspiratory neurones, in which postsynaptic potentials were well demonstrated, were characterized by an early depolarization followed by long-lasting hyperpolarization. In three other inspiratory neurones only late hyperpolarization was present. The reversal of the late hyperpolarization by intracellular chloride injection was achieved to a different degree in the early and late portions of late hyperpolarization.4. Postsynaptic potentials evoked in expiratory neurones were studied in sixteen neurones and displayed two patterns: early hyperpolarization followed by longlasting hyperpolarization (n = 7, six were not antidromically activated after spinal cord stimulation) or early hyperpolarization followed by late depolarization (n = 9, eight projected to the spinal cord). The early hyperpolarization was readily reversed by chloride injection. The late hyperpolarization was more difficult to reverse and usually the reversal was not completed.5. Postsynaptic potentials evoked in post-inspiratory neurones showed a pattern of two consecutive phases of depolarization.6. The present study revealed that during long-lasting apnoea evoked by SLN stimulation each category of VRG respiratory neurones received a temporally synchronized combination of an initial fast input derived reflexly from laryngeal MS 8566 5-2

An adenosine A2A agonist injected in the nucleus of the solitary tract prolongs the laryngeal chemoreflex by a GABAergic mechanism in decerebrate piglets

“…These findings are consistent with the hypothesis that hyperthermia increases adenosine levels in the NTS, and adenosine binds to Ad-A 2A receptors that amplify GABAergic mechanisms and prolong the LCR (Abu-Shaweesh et al 2001; Abu-Shaweesh 2007; Xia et al 2008a). These results highlight the existence of a thermally sensitive adenosinergic and GABAergic circuit in the dorsal medulla that is separate from but contributes to the ventral medullary circuit mediating respiratory inhibition associated with the LCR (Remmers et al 1986; Czyzyk-Krzeska & Lawson 1991). …”

“…Afferent information from these receptors is carried to the central nervous system by the SLN and has its primary termination on neurons in the caudal NTS (Patrickson et al 1991; Hayakawa et al 2001). From the NTS the information ramifies throughout the brainstem, and the reflex respiratory inhibition originating from sensory activation in the larynx ultimately inhibits inspiratory and expiratory neurons and stimulates post-inspiratory neurons in the region of the nucleus ambiguus in the ventral medulla (Remmers et al 1986; Czyzyk-Krzeska & Lawson 1991). Apnea after stimulation of the larynx results, therefore, from prolonged expiratory time; the post-inspiratory neurons remain persistently depolarized and prevent the normal sequential activation of expiratory neurons that would lead to the next breath (Remmers et al 1986).…”

An adenosine A2A antagonist injected in the NTS reverses thermal prolongation of the LCR in decerebrate piglets

“…This was not a chance selection; the normothermic respiratory inhibition associated with the LCR in newborn animals is integrated within the ventral respiratory group of neurons in the region of the nucleus ambiguus (Czyzyk-Krzeska and Lawson, 1991; Remmers et al, 1986). Injections into the nucleus ambiguus gave us the opportunity to determine whether the Ad-A 2A receptor antagonist affected only the thermal prolongation of the LCR or other, normothermic characteristics of the LCR as well.…”

“…Furthermore, unilateral microdialysis of gabazine (a GABA A receptor antagonist) in or near the NTS reversed the thermal prolongation of the LCR in decerebrate piglets (Xia et al, 2007), but did not change the duration of the LCR under normothermic conditions. Thus, the thermal effects on the LCR seem to depend on GABAergic mechanisms in the region of the NTS; whereas the apnea and respiratory disruption associated with superior laryngeal nerve stimulation during normothermia seem to depend on GABAergic mechanisms in the ventral medulla (Czyzyk-Krzeska and Lawson, 1991; Remmers et al, 1986; van der Velde et al, 2003). …”

“…Since GABA A receptor activation seems to be involved in the apnea and respiratory disruption of the LCR and in the thermal prolongation of the LCR, we tested the hypothesis that an antagonist of Ad-A 2A receptors focally injected within the NTS would prevent thermal prolongation of the LCR in decerebrate piglets. We chose as our anatomical control site the nucleus ambiguus, which contains neurons thought to mediate the respiratory inhibition after SLN stimulation (Czyzyk-Krzeska and Lawson, 1991; Jiang and Lipski, 1992; Remmers et al, 1986). It was our expectation that blocking Ad-A 2A receptors in the NTS would reverse thermal prolongation of the LCR, and blocking Ad-A 2A receptors in the nucleus ambiguus might shorten the LCR under normothermic conditions, but leave the thermal prolongation of the LCR intact.…”