Group II metabotropic glutamate receptor activation in the basolateral amygdala mediates individual differences in stress-induced changes in rapid eye movement sleep

Abstract

Group II metabotropic glutamate receptors (mGluR2/3s) have been implicated in stress and trauma related disorders including post-traumatic stress disorder (PTSD). PTSD is characterized by flashbacks, anxiety, and sleep disturbances. While many people are exposed to trauma in their lifetime, only a small percentage go on to develop PTSD, indicating individual differences in stress and emotional processing. Wistar strain rats display directionally different rapid-eye movement sleep (REM) responses to footshock stress, with resilient rats having no change or an increase in REM and vulnerable rats having a significant reduction in REM compared to baseline. The basolateral nucleus of the amygdala (BLA) is key in regulating individual differences in stress-induced alterations in sleep. Group II metabotropic glutamate receptors (mGluR2/3s) negatively modulate glutamate and are implicated in fear, fear memory, and sleep. The current study evaluated the effect of mGluR2/3 agonist LY379268 (LY37) in BLA on stress and fear memory induced changes in sleep, EEG spectra, behavioral fear expression and physiological stress. These data indicate that vulnerable rats treated with LY37 have an attenuation of the REM reductions generally seen in vulnerable rats. Furthermore, LY37 altered EEG spectra in the delta (0.5-4.5 Hz) and theta (5-9.5 Hz) frequency. LY37 did not impact behavioral fear expression or physiological stress. Therefore, mGluR2/3s within BLA are implicated in regulating individual differences in sleep responses to fear- and stress-related memories.

Keywords: Basolateral amygdala; Group II metabotropic glutamate receptor; PTSD; REM sleep; Stress resilience and vulnerability.