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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 alpha(2) adrenergic receptors on the cholinergic cells. Yet some 'possibly' cholinergic neurons are purportedly maximally active during waking and excited by noradrenaline through alpha(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 alpha(2A) or alpha(1A) adrenergic receptors. For comparison, we examined immunostaining for these receptors on tyrosine hydroxylase-immunopositive locus coeruleus neurons, which are known to bear alpha(2A) autoreceptors. Whereas virtually all the noradrenergic neurons were labeled for the alpha(2A) and none for the alpha(1A), approximately half the cholinergic neurons were labeled for the alpha(2A) and one third for the alpha(1A) adrenergic receptors in adjacent sections. These results suggest that different groups of cholinergic neurons bear alpha(2) versus alpha(1) adrenergic receptors and would accordingly have different sleep-wake state activities and roles. The alpha(2)-bearing group would be inhibited by noradrenaline during waking to become disinhibited and maximally active while promoting paradoxical sleep, whereas the alpha(1)-bearing group would be excited by noradrenaline during waking to become maximally active while promoting features of that state.

Basal forebrain neurons play important parts in processes of cortical activation and memory that have been attributed to the cortically projecting, cholinergic neurons. Yet, non-cholinergic neurons also project to the cerebral cortex and also appear to participate in processes of cortical modulation and plasticity. GABAergic neurons compose a portion of the cortically projecting cell group, but do not fully account for the non-cholinergic cell contingent. In the present study in the rat, we investigated whether the non-cholinergic, non-GABAergic cell component might be composed of glutamatergic neurons. We examined afferents to the entorhinal cortex, which is known to be modulated by basal forebrain neurons and to be critically involved in memory. Dual immunofluorescent staining was performed for cholera toxin, as retrograde tracer, and phosphate-activated glutaminase, the synthetic enzyme for the neurotransmitter pool of glutamate. The retrogradely labeled cells were distributed across the basal forebrain through the medial septum, diagonal band, magnocellular preoptic area and substantia innominata. The major proportion (approximately 80%) of the retrogradely labeled cells was found to be immunopositive for phosphate-activated glutaminase. Equal minor proportions (approximately 40%) were immunopositive for choline acetyltransferase and glutamic acid decarboxylase. In other material dual-immunostained for neurotransmitter enzymes, approximately 95% of choline acetyltransferase- and approximately 60% of glutamic acid decarboxylase-immunopositive neurons were also immunopositive for phosphate-activated glutaminase. From these results it appears that a significant proportion of these cell groups, including their cortically projecting contingents, could synthesize glutamate together with acetylcholine or GABA as neurotransmitters and another proportion of cells could synthesize glutamate alone. Accordingly, as either co-transmitter or primary transmitter within basalocortical afferents, glutamate could have the capacity to modulate the entorhinal cortex and promote its role in memory.