Nucleus tractus solitarii (nTS) is required for phrenic long term facilitation (pLTF) after acute intermittent hypoxia (AIH)

Abstract

Repeated episodes of acute hypoxia lead to pLTF which is thought to involve local mechanisms in the spinal cord. However, carotid body denervation decreases pLTF indicating chemoreceptor afferent input also contributes to pLTF. We hypothesized that the nTS, the first integration site of chemoreceptor afferents, is critical to the generation and maintenance of pLTF. Anesthetized, vagotomized, paralyzed and ventilated male rats were exposed to 10 hypoxic episodes (10% O2, 45sec, 5 min intervals) following bilateral nTS microinjection of aCSF or the GABA receptor agonist muscimol to inhibit nTS activity. After aCSF injection (n=4) integrated phrenic nerve activity increased during hypoxia (567±222% baseline) and amplitude remained elevated ≥1hr after AIH (131±28% baseline). Muscimol injection (2mM; 60nL) prior to AIH blocked increases in phrenic activity during hypoxia (7±14% baseline; n=3) and no LTF occurred (−3±8% baseline). Furthermore, muscimol injections after pLTF induction (130±33% baseline; n=3) decreased phrenic nerve amplitude toward pre‐AIH levels (6±10% baseline; n=3). Results indicate that nTS neuronal activity is required for the development and maintenance of pLTF. HL98602, AvH 1135664