Inhibition of serotonergic neurons in the nucleus paragigantocellularis lateralis fragments sleep and decreases rapid eye movement sleep in the piglet: implications for sudden infant death syndrome.
Serotonergic receptor binding is altered in the medullary serotonergic nuclei, including the paragigantocellularis lateralis (PGCL), in many infants who die of sudden infant death syndrome (SIDS). The PGCL receives inputs from many sites in the caudal brainstem and projects to the spinal cord and to more rostral areas important for arousal and vigilance. We have shown previously that local unilateral nonspecific neuronal inhibition in this region with GABA(A) agonists disrupts sleep architecture. We hypothesized that specifically inhibiting serotonergic activity in the PGCL would result in less sleep and heightened vigilance. We analyzed sleep before and after unilaterally dialyzing the 5-HT1A agonist (+/-)-8-hydroxy-2-(dipropylamino)-tetralin (8-OH-DPAT) into the juxtafacial PGCL in conscious newborn piglets. 8-OH-DPAT dialysis resulted in fragmented sleep with an increase in the number and a decrease in the duration of bouts of nonrapid eye movement (NREM) sleep and a marked decrease in amount of rapid eye movement (REM) sleep. After 8-OH-DPAT dialysis, there were decreases in body movements, including shivering, during NREM sleep; body temperature and heart rate also decreased. The effects of 8-OH-DPAT were blocked by local pretreatment with N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinylcyclohexane-carboxamide, a selective 5-HT1A antagonist. Destruction of serotonergic neurons with 5,7-DHT resulted in fragmented sleep and eliminated the effects of subsequent 8-OH-DPAT dialysis on REM but not the effects on body temperature or heart rate. We conclude that neurons expressing 5-HT1A autoreceptors in the juxtafacial PGCL are involved in regulating or modulating sleep. Abnormalities in the function of these neurons may alter sleep homeostasis and contribute to the etiology of SIDS.
Darnall
Robert A
RA
Department of Physiology, Dartmouth Medical School, Lebanon, New Hampshire 03756, USA. robert.a.darnall@hitchcock.org
Harris
Michael B
MB
Gill
W Hugh
WH
Hoffman
Jill M
JM
Brown
Justin W
JW
Niblock
Mary M
MM
D000818:Animals; D001931:Brain Mapping; D004195:Disease Models, Animal; D004569:Electroencephalography; D004576:Electromyography; D005260:Female; D049690:History, Ancient; D006801:Humans; D007223:Infant; D008297:Male; D008526:Medulla Oblongata / Q000033:anatomy & histology / Q000503:physiopathology*; D012893:Sleep Wake Disorders / Q000503:physiopathology*; D012895:Sleep, REM; D013238:Stereotaxic Techniques; D013398:Sudden Infant Death / Q000209:etiology*; D013552:Swine