Unilateral ablation of Pre-Bötzinger Complex disrupts breathing during sleep but not wakefulness

McKay, L. C. and Feldman, J. L. (2008) Unilateral ablation of Pre-Bötzinger Complex disrupts breathing during sleep but not wakefulness. American Journal of Respiratory and Critical Care Medicine, 178(1), pp. 89-95. (doi:10.1164/rccm.200712-1901OC)

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Publisher's URL: http://dx.doi.org/10.1164/rccm.200712-1901OC

Abstract

<b>Rationale:</b> In adult rats, bilateral ablation of pre-Bötzinger complex (preBötC) neurokinin 1–expressing (NK1R) neurons leads to a progressive and irreversible disruption in breathing pattern, initially during sleep, eventually resulting in an ataxic breathing pattern during wakefulness.<p></p> <b>Objectives:</b> Here we determine whether ablation of fewer preBötC NK1R neurons leads to a persistent pattern of disordered breathing during sleep but not during wakefulness.<p></p> <b>Methods:</b> Adult male Sprague-Dawley rats (n = 12) were instrumented to record diaphragmatic, abdominal, and neck EMG, and EEG. Fourteen days later, a second surgery was performed to stereotaxically microinject into the preBötC on one side the toxin saporin conjugated to substance P (SP-SAP), which selectively ablates NK1R neurons.<p></p> <b>Measurements and Main Results:</b> Postinjection, rats were monitored within a plethysmograph until they were killed (Days 21–51). At Days 6–9 post–unilateral SP-SAP injection, respiratory pattern during sleep, particularly REM sleep, became increasingly disordered, characterized by an increase in frequency of central sleep apnea and hypopneas (36.8 ± 7.4 episodes/h of REM vs. 6 ± 2.0 episodes/h in preinjection controls; P <0.05), whereas breathing during resting wakefulness remained stable. Unlike bilateral SP-SAP–injected rats, an ataxic breathing pattern did not develop during wakefulness. Rats that were monitored up to 51 days post–SP-SAP injection continued to have sleep-disordered breathing; breathing during wakefulness remained relatively stable. Histologic analysis of the ventrolateral medulla confirmed that NK1R neurons within the preBötC on the injected but not on the contralateral side of the medulla were ablated.<p></p> <b>Conclusions:</b> Gradual loss of preBötC NK1R neurons may be an underlying factor of sleep-disordered breathing, in particular of central sleep apnea.<p></p>

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McKay, Dr Leanne
Authors: McKay, L. C., and Feldman, J. L.
College/School:College of Medical Veterinary and Life Sciences > Institute of Neuroscience and Psychology
Journal Name:American Journal of Respiratory and Critical Care Medicine
Publisher:American Thoracic Society
ISSN:1073-449X
ISSN (Online):1535-4970
Published Online:17 April 2008

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