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Attention, prediction and sequence learning : roles of the cholinergic basal forebrain and the retrosplenial cortex


Our ability to foresee and shape biologically important events relies on a combination of visuospatial attention, memory capacities, and an ability to learn new sequences of goal-directed action. A novel set of behavioral studies were conducted to investigate neurobiological processes that underlie selective attention and visuospatial sequence learning. The first experiment assessed a theorized computational role of basal forebrain cholinergic neurons in modulating attention by increasing stimulus processing in proportion to an animal's uncertainty of impending events in the environment. A selective lesion of basal forebrain cholinergic neurons in rats produced a graded impairment in behavior that corresponds to the uncertainty elicited by different probabilistic classes of stimuli in the task. The findings thus provide initial support for a cholinergic role the regulation of Bayesian-like inference by regulating the balance of expectations and sensory processing in the brain. In a second experiment, the effects of sleep deprivation were assessed in a selective attention task to test hypothesized effects of the circadian regulation of attention through its suppressive effects on acetylcholine and other neurochemical systems. In a third experiment, the retrosplenial cortex of rats was reversibly inactivated to assess a role of the structure in temporal order learning suggested by retrosplenial pathologies in humans such as early Alzheimer's disease. The reversible inactivation of neural activity in the retrosplenial cortex produced impairments during an early, but not a late stage of visuospatial sequence learning, providing direct evidence for a memory role of the structure during the encoding of ordered events in the environment. In combination, the studies provide new insights into the biological processes that underlie the human capacities for attention, memory and sequence learning in response to new challenges in the environment

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