A striking feature of sleep is the gradual silencing of noradrenergic (NA) and serotonergic (5-HT) neurons in brainstem locus coeruleus (LC) and dorsal raphe nuclei (DRN) as an animal passes from wakefulness (W) to non-rapid-eye movement sleep (NREM) to rapid eye-movement sleep (REM). This silencing is currently thought to be necessary for REM. However, in cats with pontine lesions that create the phenomenon of REM without atonia (REM-A), DRN neurons can resume a relatively high rate of firing. In REM-A, animals can exhibit elaborate behavior (head- lifting; righting on forelimbs, """"""""orienting"""""""" [some can orient to external stimuli], standing and locomotion). Thus, the role of 5-HT during REM may involve motor aspects of state control. The fate of NA LC neurons in REM-A is unknown. In W, NA LC neurons have roles in orienting and motor behavior whereas they are silent in normal REM. This project will (l) compare REM and REM-A in rats and (2) study the activity of NA LC cells in REM and in REM-A. The latter is a state in which many electrophysiological characteristics of REM, when NA cells normally would be silent, co-occur with orienting-like behavior that, in W, could be associated with their activation. This approach will allow us to address a question fundamental to our understanding of REM: Is the silence of NA neurons necessary for REM? We shall thoroughly describe the behavior of REM-A in rats and determine their ability to respond overtly to neutral and significant external stimuli. We shall then determine the relationship of NA LC neurons to spontaneously emitted and externally elicited stimuli in REM-A. These studies will provide information as to whether the silence of these neurons is necessary for REM, or whether it is associated with the behavioral suppression created by the atonia of normal REM. These studies may lead to a better understanding of disorders of REM, such as REM behavior disorder, which, like REM-A, is characterized by overt behavior during sleep.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS036694-04
Application #
6330505
Study Section
Special Emphasis Panel (ZRG1-IFCN-3 (01))
Program Officer
Mitler, Merrill
Project Start
1999-01-01
Project End
2003-11-30
Budget Start
2000-12-01
Budget End
2003-11-30
Support Year
4
Fiscal Year
2001
Total Cost
$186,333
Indirect Cost
Name
Eastern Virginia Medical School
Department
Pathology
Type
Schools of Medicine
DUNS #
City
Norfolk
State
VA
Country
United States
Zip Code
23501
Sanford, Larry D; Yang, Linghui; Tang, Xiangdong et al. (2005) Tetrodotoxin inactivation of pontine regions: influence on sleep-wake states. Brain Res 1044:42-50
Sanford, Larry D; Tang, Xiangdong; Ross, Richard J et al. (2003) Influence of shock training and explicit fear-conditioned cues on sleep architecture in mice: strain comparison. Behav Genet 33:43-58
Sanford, Larry D; Tang, Xiangdong; Xiao, Jihua et al. (2003) GABAergic regulation of REM sleep in reticularis pontis oralis and caudalis in rats. J Neurophysiol 90:938-45
Tang, Xiangdong; Sanford, Larry D (2002) Telemetric recording of sleep and home cage activity in mice. Sleep 25:691-9
Sanford, Larry D; Parris, Brian; Tang, Xiangdong (2002) GABAergic regulation of the central nucleus of the amygdala: implications for sleep control. Brain Res 956:276-84