Corticolimbic circuits in the brain have been implicated in signaling information about expected outcomes and their general value. Yet recent work suggests that brain circuits also maintain information specific to particular outcomes and that decisions - and learning - can be driven by changes in outcome information even when value remains unchanged. Recently it was shown that outcome-specific learning depends critically on the orbitofrontal cortex and ventral striatum, and that simple value-based learning also requires ventral striatum. This suggests a new model whereby ventral striatum integrates specific information about outcomes from orbitofrontal cortex in order to generate value representations. These surprising new findings indicate that ventral striatum plays a wider role in learning than originally thought and is more consistent with the integration of outcome and value information. However, these results do not address whether this integration continues downstream in the ventral tegmental area (VTA) or whether ventral striatum might send information about cached value to the midbrain dopamine neurons but outcome information elsewhere. Therefore, we hypothesize that ventral striatum projections send information about outcome information downstream to VTA and its dopamine neurons signal errors in outcome-specific learning. To explore this, in Aim 1 we will first test whether VTA is necessary for learning driven by changes in reward identity. We predict that bilateral inactivation of VTA in rats during identity and value unblocking should disrupt learning. Consistent with this prediction, our preliminary data supports this novel role of VTA in outcome-specific learning. Furthermore, in Aim 2 we will test whether dopamine signals these errors in prediction of reward identity. We will measure terminal release of dopamine in the ventral striatum using fast-scan cyclic voltammetry (FSV) in awake behaving rats. If the midbrain dopamine neurons in VTA integrate value and identity, then we should observe phasic increases in dopamine in response to increases in value or shifts in identity. This result will be consistent with our preliminary data and with emerging evidence that dopaminergic error signals have access to information beyond cached value, providing fundamentally new information regarding the role of VTA and dopamine neurons in learning. In a constantly changing world, it is important to be able to understand the circuitry involved in helping us learn. Many psychiatric conditions, including drug addiction, may be associated with cognitive deficits that impair this ability to learn and it is critical to understand the normal biological function in order to develop more effective therapeutic treatments for patients with psychiatric disorders.

Public Health Relevance

The goal of this proposal is to determine the role of dopaminergic error signaling involved in outcome- specific learning. Many psychiatric conditions, including drug addiction, are associated with cognitive deficits that impair the ability to learn about expected outcomes and to use this updated information to guide appropriate behaviors. A better understanding of the circuitry involved in such cognitive deficits will lead to the development of more effective treatments for patients with psychiatric conditions.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
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Special Emphasis Panel (ZRG1-F02A-J (20))
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Babecki, Beth
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University of Maryland Baltimore
Anatomy/Cell Biology
Schools of Medicine
United States
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Wied, Heather M; Jones, Joshua L; Cooch, Nisha K et al. (2013) Disruption of model-based behavior and learning by cocaine self-administration in rats. Psychopharmacology (Berl) 229:493-501