Associative learning, decision-making, and addiction

National Institute On Drug Abuse

Investigators

Linked publications, trials & patents

Abstract

Substance use disorder (SUD) and other neuropsychiatric diseases involve altered learning and decision-making. The mechanism of these alterations, the circuits affected, and their significance to behavior are not well understood. We are using an animal models of SUD, associative learning and decision making to study the neural circuits mediating simple associative learning and decision-making and to identify critical changes that may underlie SUD and other co-morbid neuropsychiatric disorders. It is hoped that by better understanding these changes, we will have better models for intervention. In the current year, we have published papers and abstracts and presented data at meetings, which broadly address how neural circuits mediate associative learning and decision-making and how these processes are altered by use of addictive drugs. Several studies have focused on the role of dopamine in learning. Dopamine is linked closely to the mechanism of drugs of abuse and is also closely related to learning functions, thus understanding its role in the brain is likely central to understanding SUD. In the current year, we have published work showing that dopaminergic teaching signals reflect multithreaded predictive models, likely dependent on higher order areas. This idea dramatically expands the scope of learning dopamine may impact. This work involved close collaboration with computational modelers, which we also engaged in several other projects. In collaborative work we also have published on the role of dopamine in latent inhibition, and we published a large scale overview of dopamine function for Current Biology. In other work focused on understanding cortical processing, we published new data elaborating on the role of the orbitofrontal cortex in critical associate learning functions and in particular to the definition of task states based on hidden or partial external information. This work extends our recent proposal that the OFC functions as a "cartographer" in the construction of Tolman's cognitive maps, delineating a specific role for this area in developing or maintaining parts of the map with ambiguous or uncertain significance to rewards. Finally we have also completed work showing that cocaine use in rats leads to a selective degradation and oversimplification of the maps due to changes in orbitofrontal processing, effects mitigated byD3 agents. This work is currently in preparation for publication in several papers. Finally the lab has done well on a practical basis: 2 postdocs have secured tenure-track faculty positions and published widely, including several of the above papers in Nature Neuroscience.