Gatsby Computational Neuroscience Unit
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Supported by The Gatsby Foundation

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Cholinergic Modulation of Cortex: Attention and Plasticity

Chris C
órdova and Andrea Chiba
University of California, San Diego, USA

Numerous studies have demonstrated that the integrity of the basal forebrain cholinergic system is essential when an animal must increment attention to events with relatively unknown consequences.  From these findings, computational theorists have proposed that cholinergic neurons may optimize stimulus inference by modulating attention in proportion to the uncertainty of ongoing stimulus predictions.  In an initial test of this theory, a group of rats was trained to respond to a series of visuospatial stimuli.  Each of these stimuli was associated with a different probability of occurrence (a 2-layer HMM). consistent with computational hypotheses, rats with selective cholinergic lesions of the (Substantia Innominata/Nucleus Basalis of Meynert) SI/NBM were more impaired than control rats when responding to less predictable stimuli.  These data further support a role for the SI/NBM cholinergic projection to cortex in enhancing attention to less predictable stimuli.

Many theorists have proposed that such an enhancement of attention or learning may rely on the timely presence of acetylcholine in cortex that, in turn, permits the induction of cortical plasticity.  One realm of learning that is thought to require cortical plasticity for optimal responding to a stimulus is motor learning. In a motor learning task, rats with selective cholinergic lesions of the SI/NBM were unable to optimize their reaching performance with practice. In the absence of the cholinergic projections to cortex, the forelimb map did not expand with practice. Thus, a failure to attain optimal reaching can be attributed to a lack of cortical plasticity.

Evidence that an animal must have intact cholinergic function for performance enhancement across distinct behavioral domains suggests a more general role for the corticopetal cholinergic system in permitting cortical plasticity.  A demonstration that the SI/NBM exhibits rhythmic modulation of neural activity may provide a venue for investigating potential mechanisms underlying this plasticity.