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Role of central serotonin (5‐HT) in sleep architecture and the control of breathing during sleep in adult rats
Author(s) -
Magnusson Jennifer,
Li Aihua,
Hodges Mathew,
Cummings Kevin
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.773.3
Subject(s) - tph2 , medicine , endocrinology , ventilation (architecture) , respiratory rate , tidal volume , heart rate , tryptophan hydroxylase , wakefulness , blood pressure , respiratory system , sleep (system call) , respiratory minute volume , serotonin , anesthesia , psychology , electroencephalography , neuroscience , serotonergic , receptor , computer science , engineering , operating system , mechanical engineering
5‐HT neurons have a relatively high firing frequency during wakefulness (QW), a reduced firing rate during quiet sleep (SWS), and are essentially quiescent during rapid eye movement sleep (REMS). Studies have shown that mice lacking tryptophan hydroxylase 2 (TPH2), the rate limiting enzyme in central 5‐HT synthesis, have a reduced arterial blood pressure (BP) and breathing frequency (f B ). However, the specific role of brainstem 5‐HT in sleep architecture and cardiorespiratory regulation across sleep states is unclear. We hypothesized that, relative to control littermates, TPH2‐deficient adult rats ( TPH2 − / −) would have increased sleep, and that during QW and QS they would have reduced arterial blood pressure (BP), f B and ventilation (V E ) and a destabilized respiratory pattern relative to controls. To test these hypotheses, we used electroencephalography and electromyography to monitor the sleep state of adult rats deficient in tryptophan hydroxylase 2 ( TPH2 − / − ; n=17) and littermate controls ( TPH2 +/+ ; n=13). Femoral arterial catheters were used to measure BP and heart rate (HR), and whole body plethysmography was used to measure respiratory variables, including f B , tidal volume (V T ), ventilation (V E ), and metabolic rate (V O2 ). We also measured the coefficient of variability in breathing (CV%) as an index of respiratory stability. TPH2 − / − rats experienced episodes of REMS and SWS that, on average, were ~110s and ~40s longer than controls, respectively (p<0.0001 and p=0.028, respectively). 5‐HT deficiency had no effect on BP or HR in any sleep‐state. A loss of central 5‐HT reduced breathing f B in REM sleep (10 bpm; p<0.001), but not in QW or QS. TPH2 − / − rats had a significantly increased V T compared to controls (~0.0015ml/g ; p=0.013) but, contrary to our hypothesis, genotype had no significant effect on V E or V E /V O2 in any state. However, across all states female TPH2 − / − rats displayed a significantly destabilized breathing pattern compared to female TPH2 +/+ (p=0.003). In summary, our data suggest that central 5‐HT signaling regulates the duration of REM sleep as well as the respiratory rhythm and pattern during REM sleep. Support or Funding Information Funding for this research was provided by an American Heart Association Scientist Development Grant (14SDG18560022; PI: KJC).