The role of active zone protein Rab3 interacting molecule 1 alpha in the regulation of norepinephrine release, response to novelty, and sleep

• Published in: Neuroscience 2008-06, Vol.154 (2), p.821-831
• Main Authors: Lonart, G, Tang, X, Simsek-Duran, F, Machida, M, Sanford, L.D
• Format: Article
• Language: English
• Subjects: amygdala; Amygdala - metabolism; Animals; Behavior, Animal - physiology; Biological and medical sciences; Cerebral Cortex - metabolism; Darkness; Electroencephalography; Environment; Fundamental and applied biological sciences. Psychology; GTP-Binding Proteins - physiology; Light; Mice; Mice, Knockout; Motor Activity - physiology; Neurology; Norepinephrine - genetics; Norepinephrine - metabolism; open field; REM; Rim1αKO; Sleep - genetics; Sleep - physiology; Sleep. Vigilance; Stress, Psychological - genetics; Stress, Psychological - metabolism; Synapses - physiology; synaptic plasticity; Telemetry; Vertebrates: nervous system and sense organs
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2008.03.047

Abstract Sleep mechanisms and synaptic plasticity are thought to interact to regulate homeostasis and memory formation. However, the influences of molecules that mediate synaptic plasticity on sleep are not well understood. In this study we demonstrate that mice lacking Rab3 interacting molecule 1 alpha (RIM1α) ( Rim1αKO ), a protein of the synaptic active zone required for certain types of synaptic plasticity and learning, had 53±5% less baseline rapid eye movement (REM) sleep compared with their wild type littermates. Also, compared with wild type littermates, exposure of the mice to an open field or to a novel object induced more robust and longer lasting locomotion suggesting altered habituation. This difference in exploratory behavior correlated with genotype specific changes in REM and deregulated release of norepinephrine in the cortex and basal amygdala of the Rim1αKO mice. Also, moderate sleep deprivation (4 h), a test of the homeostatic sleep response, induced REM sleep rebound with different time course in Rim1αKO and their wild type littermates. As norepinephrine plays an important role in regulating arousal and REM sleep, our data suggest that noradrenergic deficiency in Rim1αKO animals impacts exploratory behavior and sleep regulation and contributes to impairments in learning.