The International Research Fellowship Program enables U.S. scientists and engineers to conduct nine to twenty-four months of research abroad. The program's awards provide opportunities for joint research, and the use of unique or complementary facilities, expertise and experimental conditions abroad.
This award will support a twenty-four-month research fellowship by Dr. Christopher A. Cordova to work with Dr. Barbara Jones at McGill University in Canada.
The brain's ability to discern the causal fabric of the environment arises from the appropriate allocation of attention and associative learning to predictive relations between stimuli. Cholinergic neurons in the basal forebrain exert a profound influence on neural activity and plasticity in the outlying cortex, and may play an important role in the selective processing of biologically significant events. Recent behavioral studies have suggested that cholinergic neurons increase the processing of predictive cues in proportion to the uncertainty of ongoing stimulus predictions, a strategy that is closely analogous to that of Bayesian models of learning that regulate the development of statistically optimal associations on the basis of a cumulative stimulus history. Using a novel combination of neuron recording, neurochemical labeling and behavioral techniques, a series of studies are being conducted to assess the role of the basal forebrain cholinergic system in regulating attention and learning processes in the cortex. One study characterizes the modulatory role of cholinergic neurons by recording and labeling neurons in the basal forebrain of rats while they learn probabilistic relations between cues and liquid rewards. The computational role of cholinergic neurons can thereby be assessed by relating the activity of cytochemically identified cholinergic neurons to the hypothesized uncertainty of reward predictions across different stages of learning. A variation of the task with both rewarding and aversive gustatory outcomes assesses the possibility that cholinergic neurons regulate the processing of conditioned stimuli with different valence classes with the same hypothesized measure of predictive uncertainty. Another study assesses the contributions of a major input structure to the cholinergic system by recording and labeling orexin neurons in the lateral hypothalamus during the same behavioral tasks. Orexin neurons contribute to the mediation of food drives, and play a critical role in maintaining the stable wakefulness of the brain during states of heightened arousal. The activity of orexin neurons may thus reflect anticipated rewards following the presentation of cues and could also predict aversive outcomes, reflecting a role in the regulation of cortical activity in anticipation of biologically important events. Despite their prominent regulatory roles, neither cholinergic nor orexin neurons have been recorded during a behavioral task. The use of these techniques in relatively simple learning tasks will allow an evaluation of powerful, yet untested hypotheses of neurobiological processes that regulate the waking, attentive and learning states of the cortex.
