Limbic Modulation of Arousal and Alerting

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DESCRIPTION (provided by applicant): The long-term goal of this project is to further our understanding of how emotional factors influence sleep and responsiveness to environmental stimuli. Emotional state has a major influence on how we react to the situations and events we experience, and it also has a strong influence on sleep quality and amount. This statement is both intuitive and factually supported by the observed role of emotional factors in human clinical sleep medicine and in psychiatric disorders in which sleep is affected. However the role of emotion virtually has been ignored in basic sleep research, possibly because of the lack of a clear anatomical focus, or perhaps because of a lack of established models. The amygdala, the limbic "center" of emotion, may be a key region for modulating the influence of emotion on sleep. There is a well-developed body of knowledge on the role of various amygdaloid nuclei in emotion, and emerging evidence indicating that the amygdala is a strong modulator of arousal state. We plan to selectively inactivate specific regions of the amygdala and brainstem to: 1) examine the role of amygdaloid input and output nuclei in modulating sleep and spontaneously generated neural markers of alerting. 2) examine the role of amygdaloid input and output nuclei in regulating sleep in response to fearful cues and contexts. 3) examine the role of these nuclei in modulating brain mechanisms of alerting in response to fearful cues and contexts. 4) examine the possibility that the effects of fearful cues and contexts on sleep and alerting are mediated through the locus coeruleus at the brainstem level. These studies will help elucidate how emotion, stress and the environment interact to influence sleep and responding to specific and non-specific stimuli in the environment, and they will determine the neural structures involved. These studies may provide critical insight into the development of sleep disorders which have an emotional element, such as insomnia and mental disorders in which sleep is affected. This work also may be especially relevant to posttraumatic stress disorder (PTSD), which is typically characterized by a prominent sleep disturbance in the aftermath of exposure to a psychologically traumatic stressor.