The effects of a GABA(A) agonist in the rostral ventral medulla on sleep and breathing in newborn piglets.
OBJECTIVE
Abnormalities in the rostral ventral medulla (RVM) in human infants may contribute to the etiology of the sudden infant death syndrome (SIDS) or a subset of SIDS, by interfering with cardiorespiratory and arousal responses to physiological stimuli often encountered during sleep. The purpose of this study was to determine whether inhibition of groups of neurons in the RVM in newborn piglets would alter sleep and/or the sleep-modulation of breathing. We hypothesized that inhibition of neurons in the RVM would produce less wakefulness or increase the low frequency power (delta) during Quiet sleep.


METHODS
Unanesthetized piglets were studied in a whole-body plethysmograph. Artificial cerebral spinal fluid (aCSF) or the GABAA agonist, muscimol, was dialyzed into the RVM for 40 minutes after a control period consisting of aCSF dialysis. Sleep was analyzed using a combination of EEG spectral analysis and behavioral observations.


METHODS
N/A.


METHODS
N/A.


METHODS
N/A.


RESULTS
Cardiorespiratory variables varied with state. Dialysis of neither aCSF nor muscimol into the RVM resulted in alterations in resting respiration, BP, HR, or VO2 or their modulation by state. Compared to control dialysis with aCSF, muscimol dialysis caused dramatic effects on sleep architecture. Sleep cycling was abolished in some experiments, whereas in others there were decreases in low-frequency EEG activity or delta power. The animals in which sleep cycling ceased continued in a perpetual state of drowsiness interspersed with periods of wakefulness.


CONCLUSIONS
We conclude that dialysis of muscimol into the RVM has little effect on resting breathing, blood pressure, or heart rate or their modulation by state, but interferes with normal sleep architecture. We speculate that abnormalities in the ventral medulla may alter sleep cycling or interfere with arousal mechanisms, thus contributing to the etiology of at least a subset of SIDS.
Darnall
R A
RA
Department of Physiology, Dartmouth Medical School, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA. Robert.a.darnall@dartmouth.edu
Curran
A K
AK
Filiano
J J
JJ
Li
A
A
Nattie
E E
EE
D000818:Animals; D000831:Animals, Newborn; D003645:Death, Sudden; D004569:Electroencephalography; D004576:Electromyography; D004585:Electrooculography; D018755:GABA Agonists / Q000494:pharmacology*; D008526:Medulla Oblongata / Q000187:drug effects* / Q000503:physiopathology; D009118:Muscimol / Q000494:pharmacology*; D009433:Neural Inhibition / Q000502:physiology; D012119:Respiration / Q000187:drug effects*; D012895:Sleep, REM / Q000187:drug effects*; D013552:Swine; D013997:Time Factors; D014851:Wakefulness / Q000502:physiology
D018755:GABA Agonists; D009118:Muscimol