Date of Award

Spring 2010

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biological Sciences

Program/Concentration

Biomedical Sciences

Committee Director

Larry D. Sanford

Committee Member

Gyorgy Lonart

Committee Member

J. Catesby Ware

Committee Member

Howard D. White

Abstract

Glutamate is a major excitatory neurotransmitter in the brain and it has been recognized as playing an essential role in activating and maintaining arousal. Group II metabotropic glutamate (mGlu II) receptors are expressed in the amygdala, a brain structure important in the regulation of stress and anxiety as well as in the regulation of sleep and arousal. Our lab has found that the central nucleus of the amygdala (CNA) is involved in the emotional modulation of sleep. The basal amygdala (BA), which has direct connections with the CNA, is involved in conditioned fear and fear extinction. However, the potential role of the BA in the regulation of sleep has received little attention. In this study, we investigated the role of mGlu II receptors in sleep and stress-induced alterations in sleep.

In work detailed in chapter II, either the mGlu II receptor agonist LY379268 (LY37) or antagonist LY341495 (LY34) was microinjected into the BA in rats. The effects on sleep were recorded and analyzed. It was found that LY37 suppressed rapid eye movement sleep (REM) without significantly altering non-REM sleep (NREM) or total sleep. In contrast, microinjection of LY34 at a high concentration (60 nM) increased arousal by suppressing REM and NREM.

In work detailed in chapter III, rats received conditioned fear and extinction training and LY34 or vehicle was injected into the BA immediately before fear extinction training. It was found that rats injected with LY34 demonstrated greater fear responses in the earlier periods of extinction training and showed less fear responses later in the session when compared to the control group. LY34 also ameliorated sleep disturbances following fear extinction training.

These results demonstrate that the BA may be a brain area that exerts a regulatory effect on sleep, especially REM. mGlu II receptors in the BA may be essential for regulating sleep. Suppression of these receptors may increase arousal and contribute to the improved performance of fear extinction. These data expand our knowledge on the role of the amygdala in the regulation of sleep. They may also provide prospects for the treatment of anxiety disorders, such as posttraumatic stress disorder (PTSD).

DOI

10.25777/jp4p-q462

ISBN

9781124148090

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