Bernat Kocsis1. 1. Department of Psychiatry, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. bkocsis@hms.harvard.edu
Abstract
STUDY OBJECTIVES: Sub-anesthetic doses of NMDA receptor antagonists suppress sleep and elicit continuous high-power gamma oscillations lasting for hours. This effect is subunit-specific, as it was also seen after preferential blockade of the NR2A but not of the NR2B subunit-containing receptors. The objective of this study was to test whether NR2B receptor antagonists that do not induce lasting aberrant gamma elevation affect gamma activity during specific behaviors and states, including REM sleep, when gamma normally occurs. DESIGN: Gamma oscillations in cortical EEG were assessed in different vigilance states in rats and were compared before and after injection of nonselective (ketamine, 10 mg/kg, and MK801, 0.2 mg/kg), as well as NR2A-preferring (NVP-AAM077, 20 mg/kg), and NR2B-selective NMDA receptor antagonists (Ro25-6985, 10 mg), and vehicle. MEASUREMENTS AND RESULTS: In contrast to nonselective and NR2A-preferring antagonists, Ro25-6985 did not disrupt sleep and had no effect on gamma activity during waking and slow wave sleep. It significantly increased, however, gamma power in the frontal (but not in occipital) cortex during REM sleep (by 37% ± 10%, average in the first 4 h). The effect had a short onset; enhanced gamma activity appeared as early as in the first REM sleep episode post-injection and lasted over 8 hours. Increased gamma power induced by MK-801 (46% ± 5%) and NVP-AAM077 (100% ± 8%) during REM sleep could also be detected several hours after injection when periodic alternation of sleep-wake states returned. CONCLUSIONS: By acting on gamma oscillations in a state-dependent manner, NMDA receptors might have subunit-specific role in REM sleep-associated cognitive processes.
STUDY OBJECTIVES: Sub-anesthetic doses of NMDA receptor antagonists suppress sleep and elicit continuous high-power gamma oscillations lasting for hours. This effect is subunit-specific, as it was also seen after preferential blockade of the NR2A but not of the NR2B subunit-containing receptors. The objective of this study was to test whether NR2B receptor antagonists that do not induce lasting aberrant gamma elevation affect gamma activity during specific behaviors and states, including REM sleep, when gamma normally occurs. DESIGN: Gamma oscillations in cortical EEG were assessed in different vigilance states in rats and were compared before and after injection of nonselective (ketamine, 10 mg/kg, and MK801, 0.2 mg/kg), as well as NR2A-preferring (NVP-AAM077, 20 mg/kg), and NR2B-selective NMDA receptor antagonists (Ro25-6985, 10 mg), and vehicle. MEASUREMENTS AND RESULTS: In contrast to nonselective and NR2A-preferring antagonists, Ro25-6985 did not disrupt sleep and had no effect on gamma activity during waking and slow wave sleep. It significantly increased, however, gamma power in the frontal (but not in occipital) cortex during REM sleep (by 37% ± 10%, average in the first 4 h). The effect had a short onset; enhanced gamma activity appeared as early as in the first REM sleep episode post-injection and lasted over 8 hours. Increased gamma power induced by MK-801 (46% ± 5%) and NVP-AAM077 (100% ± 8%) during REM sleep could also be detected several hours after injection when periodic alternation of sleep-wake states returned. CONCLUSIONS: By acting on gamma oscillations in a state-dependent manner, NMDA receptors might have subunit-specific role in REM sleep-associated cognitive processes.
Authors: Zhihao Mao; Shengxi He; Christopher Mesnard; Paul Synowicki; Yuning Zhang; Lucy Chung; Alex I Wiesman; Tony W Wilson; Daniel T Monaghan Journal: Brain Res Date: 2019-11-28 Impact factor: 3.252