Gatsby Computational Neuroscience Unit Alexandra House, 17 Queen Square, LONDON, WC1N 3AR, UK, Tel: +44 (0) 20 7679 1176, Fax +44 (0) 20 7679 1173 abla@gatsby.ucl.ac.uk, www.gatsby.ucl.ac.uk   ABSTRACTS Venue B10 Seminar Room, Alexandra House, 17 Queen Square London, WC1N 3AR Supported by The Gatsby Foundation |Index|Objective|Attendees|Programme|Travel information|Accommodation| Bottom-Up and Top-Down: Attentional Functions of Cortical Cholinergic inputs Martin Sarter Ohio State University, USA The available evidence clearly indicates that the integrity of cortical cholinergic inputs is necessary for attentional performance. Furthermore, attentional performance is associated with increases in cortical acetylcholine (ACh) efflux; such increases are not observed in operant control procedures which do not tax attentional demands. Furthermore, the role of basal forebrain afferent systems, particularly ascending noradrenergic projections and afferents originating in mesolimbic regions, in ‘recruiting’ the corticopetal cholinergic system in attention-demanding situations has been substantiated in recent years. However, the nature of the exact contributions of cortical cholinergic inputs to attentional performance has remained unclear. Likewise, the significance of neurophysiological evidence indicating ACh-amplification of cortical sensory input processing for the understanding of this neuronal system’s role in attentional functions has remained unsettled. Cortical cholinergic inputs are hypothesized to mediate two related aspects of attentional performance. First, mediated primarily via cholinergic inputs to prefrontal regions and the ascending modulation of the basal forebrain, attention-demanding stimuli activate the ‘anterior attention system’. Second, the anterior attention system acts to optimize, via top-down mechanisms, the processing of these stimuli. Cortical cholinergic inputs represent a major component of the neuronal circuitry mediating such top-down effects. This component of the model is supported by data indicating that the prefrontal cortex, via efferent projections to the basal forebrain and/or cortico-cortical projections, controls posterior parietal ACh efflux. This model predicts that loss of cortical cholinergic inputs prevents the ability of a stimulus to activate the anterior attention system bottom-up, and it also weakens the effectiveness of the anterior attention system to optimize the processing of this stimulus top-down. Accordingly, cortical cholinergic deafferentation is expected to impair selectively the animals’ ability to respond correctly in signal trials but to spare non-signal trial performance (e.g., McGaughy et al. 1996). Furthermore, the model predicts that increases in ACh efflux are selectively triggered by attentional stimuli; a test of this hypothesis will be possible based on new techniques that generate ACh efflux data at high temporal resolution. This model suggests that, via interacting bottom-up and top-down mechanisms, increases in cortical cholinergic activity promotes the attentional processing of a novel and salient stimulus and allows a frequently presented stimulus to “rescue itself” and thereby maintain its attentional significance. Compared to prior hypotheses, this model also allows more precise descriptions of the consequences of abnormal regulation of the cortical cholinergic input system on attentional performance and the manifestation of cognitive disorders.