GABAergic regulation of the central nucleus of the amygdala: implications for sleep control.
It is becoming established that the amygdala has a strong influence on arousal state, with most evidence indicating a role in the regulation of rapid eye movement sleep (REM). Electrically activating the central nucleus of the amygdala (CNA) can increase subsequent REM and enhance REM-related phenomena. However, drugs that may be inhibitory to CNA have been typically reported to reduce REM. This suggests that enhancing activity in CNA could promote REM, and that inhibiting activity in CNA could suppress REM. We reversibly inactivated CNA using the GABA(A) agonist, muscimol, or blocked GABAergic inhibition with the GABA(A) antagonist, bicuculline, and examined the effects on sleep and wakefulness. Rats (90-day-old male Sprague-Dawley) were implanted with electrodes for recording EEG and EMG. Cannulae were aimed into CNA for microinjecting muscimol (0.001, 0.3 and 1.0 microM/0.2 microl saline) or bicuculline (56 and 333 pM/0.2 microl saline). Each animal received bilateral microinjections of muscimol, bicuculine or saline alone followed by 6-h sleep recordings. Microinjections of low concentrations of muscimol into CNA produced relatively selective decreases in total REM and number of REM episodes that lasted up to 6 h. In contrast, microinjections of bicuculline into CNA produced significant increases in REM. There were no significant reductions in NREM or wakefulness. These findings demonstrate that inactivating CNA can produce a relatively selective suppression of REM. The possible role that spontaneous activity in CNA may play in REM initiation and/or maintenance is discussed.
Sanford
Larry D
LD
Sleep Research Laboratory, Department of Pathology and Anatomy, Eastern Virginia Medical School, PO Box 1980, Norfolk, VA 23501, USA. sanforld@evms.edu
Parris
Brian
B
Tang
Xiangdong
X
D000679:Amygdala / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D004569:Electroencephalography; D004576:Electromyography; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology*; D012890:Sleep / Q000502:physiology; D012895:Sleep, REM / Q000187:drug effects / Q000502:physiology*; D014851:Wakefulness / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D018755:GABA Agonists; D018756:GABA Antagonists; D011963:Receptors, GABA-A; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D001640:Bicuculline