Corticotropin-releasing factor mediated muscle atonia in pons and medulla.

The dorsolateral pontine inhibitory area (PIA) and medial medullary reticular formation (MMRF) have been found to mediate the muscle atonia of REM sleep. Our previous studies have shown that acetylcholine (ACh) microinjection in the PIA and in the nucleus paramedianus of the medial medulla produces muscle atonia. Glutamate microinjection in both PIA and nucleus magnocellularis (NMC) of the medial medulla also produces muscle atonia. Since immunohistochemical studies have identified corticotropin-releasing factor (CRF) as a potential dorsolateral pontine and NMC transmitter, the present study was undertaken to determine whether this transmitter could produce suppression of muscle tone. Experiments were performed on unanesthetized, decerebrated cats. CRF was microinjected into points in the PIA and NMC at which electrical stimulation produced bilateral inhibition of muscle tone. We found that CRF produced a dose-dependent muscle tone suppression. At 10 nM concentration, the latency and duration of muscle inhibition produced by CRF injection were comparable with those of L-glutamate, at 18.8 s and 4.1 min, respectively. This CRF-induced muscle inhibition was blocked by the CRF antagonist, alpha-helical [Glu27]corticotropin-releasing factor 9-41 (CRF 9-41). Microinjection of CRF and non-NMDA agonists, kainate and quisqualate, into the same sites in PIA and NMC produced muscle atonia. Pontine sites at which CRF injection induces atonia are identical to those at which acetylcholine microinjection produces atonia. These results indicate that CRF may interact with glutamate and acetylcholine in the generation of muscle atonia.