McKay LC, Feldman JL (2006) Unilateral ablation of neurokinin-1 receptor-expressing (NK1R) neurons within the preBötzinger complex (preBötC) in adult rats disrupts breathing during sleep but not during wakefulness. Neuroscience 2006 Abstracts 455.4. Society for Neuroscience, Atlanta, GA.
Summary: In adult rats, as the number of ablated preBötC NK1R neurons increases, breathing becomes increasingly disrupted during sleep(1), eventually resulting in an ataxic breathing pattern during wakefulness when cell loss is >80%(1,2). Here we determine whether ablation of fewer preBötC NKIR neurons leads to sleep-disordered breathing (SDB), while breathing during wakefulness remains stable. Adult male Sprague Dawley rats (n=8) were anesthetized (100mg/kg Ketamine, 10mg/kg Xylazine i.p.) and instrumented to record diaphragmatic, abdominal and neck EMG, ECG, and EEG. Fourteen days post-implantation a second surgery was performed to stereotaxically inject unilaterally into the preBötC, the toxin saporin conjugated to substance P (SP-SAP), which selectively ablates NK1R neurons. Rats were kept on a 12-hour light/dark cycle and monitored within a plethysmograph from day 1 post-injection until they were sacrificed (days 21-50). Post-unilateral SP-SAP injection, respiratory pattern remained normal during wakefulness and sleep until ~day 9. At this point, respiratory pattern during sleep, particularly REM sleep, became increasingly disordered. The disruptions in breathing pattern were characterised by an increase in frequency of apneas and hypopnea (~4-6/hour of sleep vs <3 pre-injection control; p<0.05). Rats that were monitored up to 50 days post-SP-SAP injection continued to have SDB, while breathing during resting wakefulness remained stable. Unlike bilateral SP-SAP injected rats, an ataxic breathing pattern did not develop during wakefulness(1,2). Histological analysis of the ventrolateral medulla confirmed that only NKIR neurons within the preBötC on one side of the medulla were ablated (~300 preBötC NK1R neurons/side in the adult rat). Unilateral SP-SAP injection results in SDB, while breathing during resting wakefulness appears normal. Over time, breathing during sleep does not improve. We have previously proposed that in the elderly and in individuals who suffer from various neurodegenerative diseases, gradual loss of preBötC NK1R neurons may explain why SDB is highly prevalent in these populations. We further speculate that SDB can go unnoticed because breathing during wakefulness is relatively stable.
Related Products: SP-SAP (Cat. #IT-07)