McKay LC, Janczewski WA, Feldman JL (2004) Ablation of NK1 receptor-expressing (NK1R) neurons within the preBötzinger complex (preBötC) in adult rats disrupts breathing during sleep before affecting breathing in wakefulness. Neuroscience 2004 Abstracts 424.9. Society for Neuroscience, San Diego, CA.
Summary: In adult rats, as the number of ablated preBÖtC NK1R neurons increases, eupnea is progressively disrupted during wakefulness, eventually resulting in an ataxic breathing pattern when cell loss is >80% (Gray et al. Nat. Neurosci. 2001). Is there a disruption of breathing during sleep prior to a disruption of breathing in wakefulness? Adult male Sprague Dawley rats (n=4) were instrumented to record: diaphragmatic, abdominal and neck EMG; ECG, and; EEG. Subsequently, the toxin Saporin conjugated to Substance P was injected bilaterally into the preBÖtC to selectively destroy NK1R neurons. Rats were monitored from day 1 postinjection until they were sacrificed between days 9-15. On days 3-4, changes in breathing pattern were observed during REM sleep. These changes were characterized by an increase in frequency of central apneas (4-7/hour vs 2/hour preinjection controls; p<0.05) and an increase in apnea length (3-6 sec vs 1-2 sec preinjection controls; p<0.05). On days 4-6, the onset of REM sleep typically induced hypopnea and a central apnea resulting in an arousal to wakefulness within 4-10 sec and the reestablishment of a normal breathing pattern. Eupnea was maintained during wakefulness; in some cases there was an increase in frequency compared to preinjection controls (183 vs 120 breaths/min). From day 6 onwards, breathing rhythm was progressively disrupted until an ataxic breathing pattern developed during wakefulness (~day 8). At this stage, rats were unable to sleep because breathing stopped upon sleep onset. In all cases, lesion extent at sacrifice, as determined by histology, was confined to the preBÖtC and >80% of NK1R neurons were destroyed. The spreading ablation of preBÖtC NK1R neurons results in a progressive disruption in breathing pattern, initially during sleep leading to pathological disturbances of breathing in both sleep and wakefulness.
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