Acute intermittent hypoxia enhances nucleus of the solitary tract neuronal activity and requires NMDARs and CaMKII for phrenic long-term facilitation.

Authors

Fatame Khodadadi-Mericle, Eileen M Hasser, David D Kline

Published in

Journal of neurophysiology. Oct 20, 2025. Epub Oct 20, 2025.

Abstract

Exposure to acute intermittent hypoxia (AIH) induces phrenic long-term facilitation (pLTF). We have shown that nucleus tractus solitarii (nTS) activity is necessary for both the development and maintenance of pLTF. Activation of glutamatergic N-Methyl-D-Aspartate receptors (NMDARs) and CaMKII contribute to in vitro long-term potentiation, nTS hypoxic responses and possibly to pLTF. This study investigated the role of nTS NMDARs and CaMKII to the development and maintenance of AIH-induced pLTF. Phrenic nerve and splanchnic sympathetic nerve activity (PhrNA and sSNA) were recorded in male Sprague-Dawley rats in response to AIH [10 bouts of 10% O₂ (45 sec, interspersed by 5 min)]. Time controls (TC) underwent a single hypoxia bout and were monitored for two hours afterward. Following AIH, PhrNA amplitude increased compared to initial baseline (BL) and TC, indicating induction of pLTF. pLTF development was associated with increased nTS neuronal Ca²⁺ and action potential discharge recorded via GCaMP8 fiber photometry and an array probe, respectively. Inhibition of nTS CaMKII activity prior to AIH exposure attenuated the development of pLTF and elevation of nTS neuronal discharge. In contrast, after pLTF had developed, inhibiting nTS CaMKII activity had no effect on the maintenance of pLTF. Nevertheless, after AIH blocking NMDARs specifically in the nTS by bilateral nanoinjection of AP5 reduced the magnitude of pLTF. Altogether, these results indicate that increased nTS neuronal activity likely due to activation of NMDARs and their downstream CaMKII signaling complex are critical components for AIH-induced neuroplasticity in central cardiorespiratory output.

PMID:
41115074
Bibliographic data and abstract were imported from PubMed on 21 Oct 2025.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.