Sleep-wake mechanisms and basal forebrain circuitry

The seminal studies by von Economo in humans (1) and by Nauta (2) in rats implicated specific basal forebrain areas at the preoptic level as important in sleep regulation. In the last two decades, studies employing recording of single neurons and monitoring of sleep parameters with subsequent chemical and electron microscopic identification of the synaptic input-output relations of these recorded neurons, provided an increasingly detailed understanding of the function of specific neurotransmitters and corresponding chemically specific neuronal circuits in the forebrain in relation to sleep-wake states. In this review, first the electrophysiology of cholinergic and parvalbumin-containing GABAergic basalo-cortical projection neurons is described, followed by an examination of possible functional interconnections between basal forebrain neuropeptide Y- (NPY) and somatostatin-containing putative interneurons and cholinergic projection neurons. A survey of various inputs to basal forebrain neurons that show state-related changes is then discussed in relation to their possible effects via basal forebrain circuitry on cortical activity. This treatise suggests that cholinergic and GABAergic projection neurons of the basal forebrain are anatomically in a unique position to enable the channeling of specific cellular and homeostatic states from different subcortical systems to the cortical mantle to modulate behavioral adaptation and cognitive functions.