Re: Retrotrapezoid nucleus: a litmus test for the identification of central chemoreceptors

Central chemoreceptors are widespread within the brain stem. We hypothesize that function at different sites varies with arousal state. In unanesthetized rats, we produced focal acidification at single sites by means of microdialysis using artificial cerebrospinal fluid equilibrated with 25% CO2. Tissue acidosis, measured under anesthesia, is equivalent to that observed with 63 Torr end-tidal Pco 2 and is limited to 600 μm. Focal acidification of the retrotrapezoid nucleus increased ventilation by 24% only in wakefulness via an increase in tidal volume (Li A, Randall M, and Nattie E. J Appl Physiol 87: 910–919, 1999). In this study of the medullary raphe, the effect of such focal acidification was in sleep (defined by electroencephalographic and electromyographic criteria): ventilation and frequency increased by 15–20% in non-rapid eye movement sleep, and frequency increased by 15% in rapid eye movement sleep. There was no effect in wakefulness. Chemoreception in the medullary raphe appears to be responsive in sleep. Central chemoreceptors at two different locations appear to vary in effectiveness with arousal state.

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CO2 dialysis in nucleus tractus solitarius region of rat increases ventilation in sleep and wakefulness

Journal of Applied Physiology ◽

10.1152/japplphysiol.01128.2001 ◽

2002 ◽

Vol 92 (5) ◽

pp. 2119-2130 ◽

Cited By ~ 107

Author(s):

Eugene E. Nattie ◽

Aihua Li

Keyword(s):

Cerebrospinal Fluid ◽

Tidal Volume ◽

Nucleus Tractus Solitarius ◽

Ventilation Frequency ◽

Retrotrapezoid Nucleus ◽

Naturally Occurring ◽

Central Chemoreceptors ◽

Artificial Cerebrospinal Fluid ◽

Medullary Raphe ◽

Stimulation Of

To evaluate the function of widely distributed central chemoreceptors during sleep and wakefulness in the rat, we focally stimulate single chemoreceptor sites during naturally occurring sleep-wake cycles by microdialysis of artificial cerebrospinal fluid equilibrated with 25% CO2. In retrotrapezoid nucleus, this increased ventilation (tidal volume) by 24% only in wakefulness (Li A, Randall M, and Nattie E. J Appl Physiol 87: 910–919, 1999). In caudal medullary raphé, it increased ventilation (frequency) by 15–20% only in sleep (Nattie EE and Li A. J Appl Physiol 90: 1247–1257, 2001). Here, in nucleus tractus solitarius (NTS), focal acidification significantly increased ventilation by 11% in sleep and 7% in wakefulness rostrally ( n = 5) and by 16% in sleep and 28% in wakefulness caudally ( n = 5). The sleep-wake cycle was unaltered. Dialysis with 5% CO2 had no effect. Dialysis with 50% CO2 caudally did not further stimulate ventilation but did disrupt sleep. Central chemoreceptors in the NTS affect breathing in both sleep and wakefulness. The threshold for arousal in caudal NTS is greater than that for the stimulation of breathing.

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CO2 microdialysis in retrotrapezoid nucleus of the rat increases breathing in wakefulness but not in sleep

Journal of Applied Physiology ◽

10.1152/jappl.1999.87.3.910 ◽

1999 ◽

Vol 87 (3) ◽

pp. 910-919 ◽

Cited By ~ 92

Author(s):

Aihua Li ◽

Margaret Randall ◽

Eugene E. Nattie

Keyword(s):

Control System ◽

Respiratory Control ◽

Semipermeable Membrane ◽

Ph Change ◽

Microdialysis Probe ◽

Retrotrapezoid Nucleus ◽

Central Chemoreceptors ◽

End Tidal ◽

The Brain ◽

Behavioral Criteria

Central chemoreceptors are widespread within the brain stem. We suggest that their function at some sites may vary with the state of arousal. In this study, we tested the hypothesis that the function of chemoreceptors in the retrotrapezoid nucleus (RTN) varies with sleep and wakefulness. In unanesthetized rats, we produced focal acidification of the RTN by means of a microdialysis probe (tip containing the semipermeable membrane = 1-mm length, 240-μm diameter, and 45-nl volume). With the use of a dialysate equilibrated with 25% CO2, the tissue pH change (measured in anesthetized animals) was 1) limited to within 550 μm of the probe and, 2) at the probe tip, was equivalent to that observed with end-tidal[Formula: see text] of 63 Torr. This focal acidification of the RTN increased ventilation significantly by 24% above baseline, on average, in 13 trials in seven rats only during wakefulness. The effect was entirely due to an increase in tidal volume. During sleep defined by behavioral criteria, ventilation was unaffected, on average, in 10 trials in seven rats. During sleep, the chemoreceptors in the RTN appear to be inactive, or, if active, the respiratory control system either is not responding or is responding with very low gain. Because ventilation is increased during sleep with all central chemoreceptor sites stimulated via systemic CO2 application, other central chemoreceptor locations must have enhanced effectiveness.

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