Involvement of GABAergic mechanisms in the laterodorsal and pedunculopontine tegmental nuclei (LDT-PPT) in the promotion of REM sleep

Abstract

The neurons of the laterodorsal and pedunculopontine tegmental nuclei (LDT-PPT) have a dual function in the control of behavioral states: they promote either wakefulness (W) or REM sleep. During W, these neurons are also related to cognitive and motor functions. In fact, the PPT is the main output station of the basal ganglia circuit and has a major role in the akinesia of Parkinson's disease (PD). Interest in this area has grown tremendously following recent demonstrations that the PPT is a promising target for treating PD symptoms by deep brain stimulation. Further progress in treating PD will be greatly assisted by a clear understanding of the structure and function of the LDT-PPT. Cholinergic neurons are the principal mediators of activity originating in the LDT-PPT. These neurons project widely to the forebrain and brainstem and increase their firing rate either during W and REM sleep or during REM sleep exclusively. Microinjections of cholinergic agonists into the nucleus pontis oralis, which is a recipient of LDT-PPT cholinergic neuronal projections, prolongs the duration of the REM sleep state. Although GABAergic neurons in the LDT-PPT outnumber cholinergic neurons by two to one, the function of these neurons is mostly unknown. These neurons may have local functions such as controlling the input and the output of cholinergic neurons; however, these cells also project outside the LDT-PPT. Utilizing Fos immunoreactivity as a marker of neuronal activity, it was shown in cats and rats that GABAergic neurons of the LDT-PPT are active during REM sleep. In addition, microinjections of muscimol (GABAA agonist) within this area generate REM sleep both in cats and rats; on the contrary, GABAA antagonists induce W. These data suggest that GABAergic neurons of the LDT-PPT promote REM sleep. In the present report, we review the role of GABA within the LDT-PPT in REM sleep regulation.