The dorsolateral pons and medial medulla have been implicated in the loss of muscle tone (atonia) of REM sleep and cataplexy. However, the synaptic organization of this ponto-medullary system is largely unknown. Indeed the anatomical localization of the medullary neurons involved in this circuit is unclear. Furthermore, while cholinergic mechanisms in the pons have been implicated in the triggering of atonia, there has been no study showing elicitation of atonia by chemical stimulation of the medulla. Thus, the transmitters activating these neurons are also unknown. We propose to identify transmitter agonists and antagonists capable of triggering or blocking atonia when microinjected at the medullary level, and map the effective sites. We have strong pilot data demonstrating that the medulla contains at least two pharmacologically and anatomically distinct regions which mediate atonia. We propose to use anatomical and electrophysiological techniques to identify the interconnections between pontine and medullary """"""""inhibitory"""""""" regions. Using extracellular and intracellular recording techniques, we propose to identify medullary cell populations selectively active during atonia and determine the inputs, outputs and morphology of these cells. We have recently found that variables linked to blood pressure have a key role in the regulation of atonia in both the decerebrate and narcoleptic animal. We have hypothesized that central chemoreceptor activity is critically involved in the triggering of atonia. Accordingly, we will investigate the relation of circulatory variables and central chemoreceptors to the activity of the pontomedullary atonia generating system. These studies will take advantage of the rapid progress that can be made in the decerebrate preparation, to analyze the ponto- medullary inhibitory circuit. They should provide important basic information on the mechanisms controlling muscle tone, and lead to a better understanding of the generation of atonia in normal REM sleep and in cataplexy.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL041370-03
Application #
3359126
Study Section
Neurosciences Research Review Committee (BPN)
Project Start
1988-08-01
Project End
1993-07-31
Budget Start
1990-08-01
Budget End
1991-07-31
Support Year
3
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Type
Other Domestic Higher Education
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Lyamin, Oleg I; Mukhametov, Lev M; Siegel, Jerome M (2017) Sleep in the northern fur seal. Curr Opin Neurobiol 44:144-151
Ramanathan, Lalini; Hu, Shuxin; Frautschy, Sally A et al. (2010) Short-term total sleep deprivation in the rat increases antioxidant responses in multiple brain regions without impairing spontaneous alternation behavior. Behav Brain Res 207:305-9
Thannickal, Thomas C; Nienhuis, Robert; Siegel, Jerome M (2009) Localized loss of hypocretin (orexin) cells in narcolepsy without cataplexy. Sleep 32:993-8
Siegel, Jerome M (2009) Sleep viewed as a state of adaptive inactivity. Nat Rev Neurosci 10:747-53
John, Joshi; Ramanathan, Lalini; Siegel, Jerome M (2008) Rapid changes in glutamate levels in the posterior hypothalamus across sleep-wake states in freely behaving rats. Am J Physiol Regul Integr Comp Physiol 295:R2041-9
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Burgess, Christian; Lai, Diane; Siegel, Jerome et al. (2008) An endogenous glutamatergic drive onto somatic motoneurons contributes to the stereotypical pattern of muscle tone across the sleep-wake cycle. J Neurosci 28:4649-60
Taepavarapruk, N; Taepavarapruk, P; John, J et al. (2008) State-dependent changes in glutamate, glycine, GABA, and dopamine levels in cat lumbar spinal cord. J Neurophysiol 100:598-608
Siegel, Jerome M (2008) Do all animals sleep? Trends Neurosci 31:208-13
Thannickal, Thomas C; Lai, Yuan-Yang; Siegel, Jerome M (2008) Hypocretin (orexin) and melanin concentrating hormone loss and the symptoms of Parkinson's disease. Brain 131:e87

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