Modulation of cognitive processes by transsynaptic activation of the basal forebrain

Each of the neurotransmitter-specific afferents to the basal forebrain (BF) carry different types of information which converge to regulate the activity of cholinergic projections to telencephalic areas. Brainstem monoaminergic and cholinergic inputs are critical for context-dependent arousal. GABAergic afferents are gated by a variety of ascending and descending systems, and in addition provide an intrinsic control of BF output excitability. Corticofugal glutamatergic inputs represent reciprocal connections from sites to which BF afferents project, and carry information about the current level of cortical processing intensity and capacity. Peptidergic inputs arise from hypothalamic sources and locally modulate BF output as a function of motivational and homeostatic processes. The significance of these afferent systems can be studied by examining the behavioral consequences of infusion into the BF of drugs that act on the specific receptor systems. Although traditional analyses suggest that the BF has many behavioral functions that can be subdivided regionally, an analysis of studies employing transsynaptic approaches lead to the conceptualization of the BF as having a uniform function, that of maximizing cortical processing efficiency. The BF is conditionally active during specific episodes of acquisition and processing of behaviorally significant, externally-derived information, and drives cortical targets into a state of readiness by reducing interference and amplifying the processing of relevant stimuli and associations, thus allowing for more efficient processing. This paper describes the transsynaptic approach to studying BF function, reviews the neurobiological and behavioral consequences of altering neurotransmitter-specific inputs to the BF, and explores the functional significance of the BF.