Endogenous excitatory drive to the respiratory system in rapid eye movement sleep in cats

Abstract

A putative endogenous excitatory drive to the respiratory system in rapid eye movement (REM) sleep may explain many characteristics of breathing in that state, e.g. its irregularity and variable ventilatory responses to chemical stimuli. This drive is hypothetical, and determinations of its existence and character are complicated by control of the respiratory system by the oscillator and its feedback mechanisms. In the present study, endogenous drive was studied during apnoea caused by mechanical hyperventilation. We reasoned that if there was a REM‐dependent drive to the respiratory system, then respiratory activity should emerge out of the background apnoea as a manifestation of the drive. Diaphragmatic muscle or medullary respiratory neuronal activity was studied in five intact, unanaesthetized adult cats who were either mechanically hyperventilated or breathed spontaneously in more than 100 REM sleep periods. Diaphragmatic activity emerged out of a background apnoea caused by mechanical hyperventilation an average of 34 s after the onset of REM sleep. Emergent activity occurred in 60 % of 10 s epochs in REM sleep and the amount of activity per unit time averaged approximately 40 % of eupnoeic activity. The activity occurred in episodes and was poorly related to pontogeniculo‐occipital waves. At low CO2 levels, this activity was non‐rhythmic. At higher CO2 levels (less than 0.5 % below eupnoeic end‐tidal percentage CO2 levels in non‐REM (NREM) sleep), activity became rhythmic. Medullary respiratory neurons were recorded in one of the five animals. Nineteen of twenty‐seven medullary respiratory neurons were excited in REM sleep during apnoea. Excited neurons included inspiratory, expiratory and phase‐spanning neurons. Excitation began about 43 s after the onset of REM sleep. Activity increased from an average of 6 impulses s−1 in NREM sleep to 15.5 impulses s−1 in REM sleep. Neuronal activity was non‐rhythmic at low CO2 levels and became rhythmic when levels were less than 0.5 % below eupnoeic end‐tidal levels in NREM sleep. The level of CO2 at which rhythmic neuronal activity developed corresponded to eupnoeic end‐tidal CO2 levels in REM sleep. These results demonstrate an endogenous excitatory drive to the respiratory system in REM sleep and account for rapid and irregular breathing and the lower set‐point to CO2 in that state.

Emerging principles and neural substrates underlying tonic sleep-state-dependent influences on respiratory motor activity

“…However, this concept was first identified in physiological experiments investigating the control of intercostal muscles. Hypocapnia produced by constant mechanical hyperventilation in anaesthetized (Sears et al 1982) or conscious (Horner et al 1994a,b;Orem et al 2000) animal preparations reveals a background tonic drive to the intercostal nerves and muscles independent of respiratory-related activity. Most relevant to this discussion, these studies showed for the first time that the tonic drive to respiratory muscle could be identified and studied independently of spontaneous respiratory rhythm in an intact conscious organism (Horner et al 1994a,b).…”

Precise rhythmicity in activity of neocortical, thalamic and brain stem neurons in behaving cats and rabbits

“…The database for this study was a subset from the databases used for our previously published studies [6,7,8,9,49,50,60]. The selection of the neurons and neuronal populations for this study was based on the duration of available spike trains (4000-65000 spikes).…”

“…The procedures of surgical preparation of the animals were described previously [7,50,52]. Surgery was performed under isoflourane (cats, 2-5%), halothane (cats, 1-2%), or pentobarbital sodium (rabbits, 25-35 mg/kg) anesthesia using aseptic procedures.…”

“…1C). After getting habituated to this experimental apparatus, the animals typically passed through phases of quiet wakefulness, non-REM sleep, and REM sleep [50].…”

“…The relation of spike activity of these neuronal populations to locomotion and respiration we have described in a series of separate reports: [6] -cat ventrolateral thalamus; [7] -cat parietal cortex; [9,60] -cat motor cortex; [8] -rabbit motor cortex; [49,50] -cat respiratory medulla. The database for this study was a subset from the databases used for the above published studies.…”