Dynamic changes in GABAA receptors on basal forebrain cholinergic neurons following sleep deprivation and recovery

Department of Neurology and Neurosurgery, McGill University, Montreal Neurological Institute, Montreal, Quebec, Canada. <>
BMC Neuroscience (Impact Factor: 2.67). 02/2007; 8(1):15. DOI: 10.1186/1471-2202-8-15
Source: PubMed


The basal forebrain (BF) cholinergic neurons play an important role in cortical activation and arousal and are active in association with cortical activation of waking and inactive in association with cortical slow wave activity of sleep. In view of findings that GABAA receptors (Rs) and inhibitory transmission undergo dynamic changes as a function of prior activity, we investigated whether the GABAARs on cholinergic cells might undergo such changes as a function of their prior activity during waking vs. sleep.
In the brains of rats under sleep control (SC), sleep deprivation (SD) or sleep recovery (SR) conditions in the 3 hours prior to sacrifice, we examined immunofluorescent staining for beta2-3 subunit GABAARs on choline acetyltransferase (ChAT) immunopositive (+) cells in the magnocellular BF. In sections also stained for c-Fos, beta2-3 GABAARs were present on ChAT+ neurons which expressed c-Fos in the SD group alone and were variable or undetectable on other ChAT+ cells across groups. In dual-immunostained sections, the luminance of beta2-3 GABAARs over the membrane of ChAT+ cells was found to vary significantly across conditions and to be significantly higher in SD than SC or SR groups.
We conclude that membrane GABAARs increase on cholinergic cells as a result of activity during sustained waking and reciprocally decrease as a result of inactivity during sleep. These changes in membrane GABAARs would be associated with increased GABA-mediated inhibition of cholinergic cells following prolonged waking and diminished inhibition following sleep and could thus reflect a homeostatic process regulating cholinergic cell activity and thereby indirectly cortical activity across the sleep-waking cycle.

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Available from: Barbara E Jones, Sep 18, 2014
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    • "The PAG contains a dense plexus of cholinergic nerve terminals derived from the pontine tegmentum; these nerves mediate analgesia at least partly via the endocannabinoid signaling system [37]. The sleep-wake cycle also controls the activity of cholinergic neurons in the basal forebrain [38]. Thus, further studies are needed to characterize the neuronal pathways that are associated with sleep deprivation-induced hyperalgesia. "
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    • "Although they would accordingly not pace slow delta EEG activity, the GABAergic BF neurons could nonetheless inhibit pyramidal cells or particular interneurons in the cortex (Henny and Jones, 2008) in a manner to prevent fast cortical activity and thereby favor slow wave activity that is generated by cortical and thalamic oscillatory networks (Steriade et al., 1994). As projection or interneurons, GABAergic S-max active neurons could also through local projections inhibit BF WP-max active cells, including the cholinergic neurons, whose activity can be homeostatically regulated through dynamically changing GABA A receptors (Modirrousta et al., 2007). "
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