Immunostaining of cholinergic pontomesencephalic neurons for α1 versus α2 adrenergic receptors suggests different sleep-wake state activities and roles

Abstract Cholinergic neurons of the pontomesencephalic tegmentum play a critical role in paradoxical sleep, when, according to single unit recording of ‘possibly’ cholinergic neurons, they fire maximally. The profile of activity of the cholinergic neurons may be determined by noradrenergic locus coeruleus neurons that are active during waking and silent during paradoxical sleep. Indeed, a permissive role of the noradrenergic neurons in paradoxical sleep has been proposed based upon an inhibitory action of noradrenaline through α 2 adrenergic receptors on the cholinergic cells. Yet some ‘possibly’ cholinergic neurons are purportedly maximally active during waking and excited by noradrenaline through α 1 receptors. In the present study, we examined by fluorescent dual-immunostaining in the laterodorsal and pedunculopontine tegmental nuclei of the rat whether choline acetyltransferase-immunopositive neurons are stained for α 2A or α 1A adrenergic receptors. For comparison, we examined immunostaining for these receptors on tyrosine hydroxylase-immunopositive locus coeruleus neurons, which are known to bear α 2A autoreceptors. Whereas virtually all the noradrenergic neurons were labeled for the α 2A and none for the α 1A , approximately half the cholinergic neurons were labeled for the α 2A and one third for the α 1A adrenergic receptors in adjacent sections. These results suggest that different groups of cholinergic neurons bear α 2 versus α 1 adrenergic receptors and would accordingly have different sleep–wake state activities and roles. The α 2 -bearing group would be inhibited by noradrenaline during waking to become disinhibited and maximally active while promoting paradoxical sleep, whereas the α 1 -bearing group would be excited by noradrenaline during waking to become maximally active while promoting features of that state.